Crystallized diacetylenic indicator compounds and methods of preparing the compounds

ABSTRACT

Crystallized diacetylenic compounds having certain crystallographic and other characteristics; diacetylenic compounds and mixtures crystallized from diacetylenic solutions; methods of preparing and identifying solvent systems for dissolving diacetylenic compounds; diacetylenic solutions; methods of recrystallizing diacetylenic compounds; crystals of 2,4-hexadiyn-1,6-bis(alkylurea) compounds; and ambient condition indicators and time-temperature condition indicators comprising crystallized diacetylenic compounds.

CROSS-REFERENCE TO A RELATED APPLICATION

This application claims the priority of provisional patent ApplicationNo. 60/983,828 filed Oct. 30, 2007 (attorney docket no. 0820887.00101)the entire disclosure of which is incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

(Not applicable.)

The present invention relates to new crystallized diacetylenic compoundsand to methods of preparing the compounds. The herein described methodsand products are generally useful in relation to diacetylenic compounds,or monomers, employable as active agents in visual indicators ofexposure to environmental conditions, for example conditions such astemperature that relate to the shelf life, freshness, maturity or othercharacteristic of a host product.

BACKGROUND

Various diacetylenic monomers that undergo a solid-state polymerizationreaction giving rise to color development, or another visually apparentchange, in a predictable and irreversible manner, have long been used asactive agents in time-temperature and other ambient conditionindicators. Such indicators can provide a simple visual indication ofthe cumulative exposure of a host product to an environmental condition.They may be used to monitor the useful shelf life of perishable hostproducts such as a foodstuff, vaccine, medicament or the like, which canbe adversely affected by inappropriate ambient temperatures or otherconditions of their surroundings or storage environment. The indicatorsystem can comprise a label incorporating the diacetylenic monomer as anactive agent. The label can be affixed to the host product or to itspackaging or otherwise associated with the host product, or can beembodied in some other convenient form.

In the polymerization reaction, many diacetylenic molecules are chainedtogether to form a polydiacetylene. This reaction takes place in thesolid state and is irreversible. In some cases, colorless or nearlycolorless crystals of the diacetylenic compound, a monomer in thiscontext, transform into intensely colored crystals of polymer inresponse to sufficient cumulative exposure to heat or anotherenvironmental condition. The polymerization reaction proceedsspontaneously, at rates largely determined by the ambient conditions.

The color change resulting from the polymerization reaction isirreversible. This property makes the compounds useful for monitoringperishable products such as food or medicines that may lose freshnessafter excessive cumulative exposure to heat. Diacetylenic monomers canalso be employed as the active agents in indicators used for monitoringthe maturity of maturing products, for example wine or cheese. For theseand other purposes, the diacetylenic monomer can be incorporated as theactive agent in an indicator label to be associated with a host productto be monitored. The indicator label provides a color change, derivedfrom polymerization of the diacetylenic monomer, which can be perceivedby a human viewer at a convenient viewing distance, for example by ashopper inspecting a refrigerated display in a supermarket. A reversibleindicator would not be useful for these purposes.

In order to effectively track possible changes in the host product itcan be desirable for the diacetylenic monomer employed to have responseparameters to heat, or to another ambient condition being monitored,that may approximately correlate with the response parameters theintended host product has to the same ambient or environmentalcondition. For this purpose, it would be useful for the indicatorformulator to have a wide range of commercially useful diacetylenicmonomers providing a variety of response parameters from which to choosea suitable monomer for monitoring a particular host product.

Many polymerizable diacetylenic compounds are known or have beensuggested, some of which provide useful color changes uponpolymerization, see for example Patel U.S. Pat. Nos. 3,999,946;4,189,399 and 4,384,980 and Preziosi et al. U.S. Pat. Nos. 4,789,637 and4,788,151. However, only a limited number of these compounds exhibitperformance parameters that render them useful for monitoring aperishable or maturing commercial product. The limited number of usefuldiacetylenic compounds that is commercially available restricts thechoice of response parameters an indicator formulator has when seeking adiacetylenic monomer to use as an active indicator agent.

Accordingly, the art includes proposals for modifying the reactivity ofa given commercially useful diacetylenic monomer so that it respondsdifferently to a given ambient condition, so as to give the formulatormore choices.

For example, U.S. Pat. No. 4,788,151 to Preziosi et al. disclosesdissolving two or more diacetylenic compounds in a heated common solventand recrystallizing the solvated compounds to produce a co-crystallizedcomposition. The co-crystallized composition has a reactivity differentfrom that of the individual compounds.

International Publication No. WO 2004/077097 to JP Laboratoriesdiscloses radiation sensitive devices, such as a film, sticker or badgefor monitoring a dose of high-energy radiations utilizing radiationsensitive materials, such as diacetylenes. As described in WO2004/077097, diacetylenes are known to crystallize into more than onecrystallographic modification or phase, and by selecting a propersolvent system, some diacetylenes, can be crystallized into a phasewhich would have extremely low thermal reactivity and a high radiationreactivity.

Also, Prusik et al. U.S. Pat. No. 6,924,148 discloses refluxing asolution of an acetylenic agent to vary its reactivity. Some examples inthe patent describe the use of glacial acetic acid and dimethylformamide as solvents for the purpose. A number of other solvents arealso disclosed as employable in the practice of the described invention.However, specific information regarding the solubilities of diacetyleniccompounds in such other solvents does not appear to be provided. SomeX-ray diffraction data are provided for one diacetylenic monomercompound.

Furthermore, U.S. Pat. No. 7,019,171 to Prusik et al. disclosesnon-comminutive processes for favorably influencing particle size inacetylenic agent crystallization processes. Some described examplesemploy solutions of acetylenic agents in acetic acid and varioussolvents such as aqueous methanol and ethyl 3-ethoxypropionate aredescribed as useful as a precipitation or quenching fluid.

In addition, U.S. Patent Publication No. 2008/0004372 (application Ser.No. 11/427,589) to Prusik et al. discloses use of a reactivity-enhancingadjuvant to adapt the reactivity of a diacetylenic indicator agent.

Notwithstanding the various known diacetylenic monomers and methods ofproviding diacetylenic monomers with modified reactivities, it would bedesirable to have more diacetylenic monomer reactivity optionsavailable, and to have new methods and products for providingdiacetylenic monomers with new or modified reactivities.

The foregoing description of background art may include insights,discoveries, understandings or disclosures, or associations together ofdisclosures, that were not known to the relevant art prior to thepresent invention but which were provided by the invention. Some suchcontributions of the invention may have been specifically pointed outherein, whereas other such contributions of the invention will beapparent from their context. Merely because a document may have beencited here, no admission is made that the field of the document, whichmay be quite different from that of the invention, is analogous to thefield or fields of the present invention.

SUMMARY OF THE INVENTION

The present invention provides, inter alia, crystallized diacetyleniccompounds in a new or modified reactivity state. The crystallizeddiacetylenic compound can be one or more compounds which provide anirreversible appearance change in an environmental condition indicator,for example a cumulative time-temperature indicator. The appearancechange can, for example, be a change in color, intensity or darkness ofthe appearance of the compound or compounds.

The invention also provides methods of preparing crystallizeddiacetylenic compounds and solvent systems and diacetylenic solutionsuseful in these methods.

In one aspect the invention provides a crystallized diacetyleniccompound capable of providing an irreversible appearance change in anenvironmental condition indicator, the crystallized diacetyleniccompound having a crystal structure comprising a polymerizablediacetylenic monomer of structural formula

R¹C≡C—C≡CR²

wherein each of R¹ and R² independently is an organic substituentcompatible with providing the irreversible appearance change. Thepolymerizable diacetylenic monomer molecules can have a center-to-centerseparation, referring to the geometric centers of adjacent unit cells ofthe crystal, of less than 4.7 Å, the center-to-center separation beingin a direction wherein solid-state polymerization can occur.

Each of R¹ and R² independently can be —R⁴NHCONHR³ where R³ is alkylhaving from 1 to 20 carbon atoms, optionally ethyl, propyl, butyl,octyl, dodecyl or octadecyl and R⁴ is alkyl having from 1 to 20 carbonatoms. Alternatively, each of R¹ and R² independently can be—CH₂NHCONHR³ where R³ is alkyl, optionally ethyl, propyl, butyl, octyl,dodecyl or octadecyl.

Where R¹ and R² each comprise a —NHCONH— group, the crystallizeddiacetylenic compound can comprise two hydrogen bonds for each ureagroup, each one of the two hydrogen bonds extending between one of thetwo NH groups on one polymerizable diacetylenic molecule and a C═O groupin a neighboring polymerizable diacetylenic molecule.

If desired, the polymerizable diacetylenic monomer can be symmetricallysubstituted and optionally can have a crystal structure wherein thediacetylene compound has a center of symmetry and no axes or planes ofsymmetry exist. The structure of a crystal having no axes or planes ofsymmetry is generally described as “triclinic”.

The crystallized diacetylenic compound agent can optionally comprise atleast one non-acetylenic compound in the crystal phase, the at least onenon-acetylenic compound optionally being a solvent or solvents. Asstated, the crystallized diacetylenic compound, or monomer, canpolymerize to provide an indicator response, for example a color change,in response to ambient heat. Desirably, the crystallized diacetyleniccompound comprises not more than about 10 percent by weight, of thepolymerized diacetylenic compound based upon the weight of thediacetylenic compound and the polymer. The proportion of polymer can forexample be not more than about 3 percent or not more than about 1percent or lower.

The invention also provides, in a further aspect, a crystallizeddiacetylenic compound having a crystal size in a first direction ofgreater than about 100 microns and a maximum dimension in a seconddirection perpendicular to the first direction of not more than about 10microns.

In another aspect the invention provides a crystallized diacetyleniccompound having the structural formula

CH₃CH₂HNCONH—CH₂—C≡C—C≡C—CH₂—NHCONHCH₂CH₃

and having a triclinic crystal structure. The compound can have acentrosymmetric crystal phase wherein the centrosymmetric crystal phasehas unit cell parameters of a=about 4.2 Å, b=about 4.6 Å, c=about 16.5Å, α=about 89° β=about 85°, and γ=about 81°.

The invention also provides, in a further aspect, a crystal of a2,4-hexadiyn-1,6-bis(alkylurea) compound exhibiting an X-ray diffractionpattern comprising two high intensity peaks at low 2θ diffraction anglesof less than about 15 degrees. The diffraction pattern also comprisesless than four high intensity peaks at high 2θ diffraction angles in therange of from about 19 degrees to about 24 degrees, when characterizedusing X-ray at a wavelength of about 1.54 Å. In one embodiment of thisaspect of the invention, the X-ray diffraction pattern comprises no highintensity peaks at high 2θ diffraction angles in the range of from about19 degrees to about 24 deg.

The 2,4-hexadiyn-1,6-bis(alkylurea) compound can, for example, be2,4-hexadiyn-1,6-bis(propylurea) or 2,4-hexadiyn-1,6-bis(ethylurea) andcan be recrystallized from a solution of2,4-hexadiyn-1,6-bis(propylurea) or 2,4-hexadiyn-1,6-bis(ethylurea),respectively, in a mixture of water with ethyl alcohol, with isopropylalcohol, with dimethyl sulfoxide or with another suitable solvent.

In addition, the invention provides, in a still further aspect, acrystal of a 2,4-hexadiyn-1,6-bis(alkylurea) compound recrystallizedfrom a solvent system, the crystal exhibiting an X-ray diffractionpattern comprising two high intensity peaks at low 2θ diffraction anglesof less than 12 degrees and comprising no more than four high intensitypeaks at high 2θ diffraction angles in the range of from about 19degrees to about 24 degrees wherein the high angle diffraction patternis determined by the solvent system employed for recrystallization.

Crystallized diacetylenic compounds according to the invention can havea relatively high purity, for example being at least about 99.8 percentby weight pure, or can be less pure, for example being at least about 90percent by weight pure.

Crystallized diacetylenic compounds according to the invention can beprepared by any suitable method, for example by crystallizing thediacetylenic compound from a diacetylenic solution of the diacetyleniccompound in a solvent system.

If desired, the diacetylenic solution can be prepared by dissolving thediacetylenic compound in the solvent system and the diacetyleniccompound, optionally, can comprise an unpurified crystallizationproduct.

The invention also includes an ambient condition indicator, optionally atime-temperature indicator or a high energy radiation monitor, whichcomprises a crystallized diacetylenic compound, or a crystallizeddiacetylenic agent as described herein, the at least one crystallizeddiacetylenic compound or agent providing a visual appearance change inresponse to exposure to an ambient condition.

In another aspect, the invention provides a time-temperature indicatorcomprising a solid phase composition including a diacetylene having thestructural formula

[CH₃(CH₂)_(n)NHCONH(CH₂)_(m)C≡C—]₂

the diacetylene being capable of polymerizing by a reaction betweenmolecules of the diacetylene wherein a C═O group on one moleculehydrogen bonds to two NH groups on an adjacent molecule and wherein:

-   -   “m” is an odd number from 1 to 7;    -   “n” is an odd number from 1 to 19; and    -   the solid phase comprises a triclinic space group P-1.

In an alternative aspect of the invention “n” is an even number from 2to 20 rather than an odd number and the solid phase comprises amonoclinic space group P2₁/a or P21/c wherein the b axis is the 2₁ axisrather than a triclinic space group P-1.

In some embodiments of the invention, the solvent system has a polarsolubility parameter in the range of from about 6 MPa^(1/2) to about 17MPa^(1/2) and has a hydrogen bond solubility parameter in the range offrom about 7.5 MPa^(1/2) to about 26 MPa^(1/2), provided that thesolvent system does not consist of acetic acid, dimethyl formamide orpyridine as the sole component of the solvent system.

By choosing solvents with the solubility parameters specified, new anduseful solvent systems for diacetylenic monomers can be identified andthe available range of solvent systems providing a desired diacetylenicsolubility can be increased.

By identifying a new crystal phase or form for a given diacetylenicmonomer the invention can enable the scope of potential commercialapplications for the diacetylenic monomer to be expanded. In someinstances a new crystal phase or form can provide a new set oftime-temperature parameters for reaction, providing a correspondinglyincreased ability to match the time-temperature characteristics for thedegradation of perishable products or the desired degree of maturationfor maturing products.

The invention also provides, in additional aspects, methods useful foridentification of one or more new solvent systems for a diacetyleniccompound which solvent systems have novel combinations of propertiessuch as ability to solubilize one or more useful diacetylenic compounds,environmental compatibility properties or useful combinations of theseor other properties.

The invention also provides various methods of preparing a diacetylenicsolution. One method comprises devising a solubility map depictingsolvents by their solubility parameters and using the solubility map toidentify and select prospective solvent components of a solvent systemfor a diacetylenic monomer to be dissolved. Another method comprisesdissolving a diacetylenic compound or diacetylenic compounds in one ofthe novel solvent systems disclosed herein wherein the dissolveddiacetylenic compound or diacetylenic compounds comprise or comprisesthe raw product of crystallization from a synthesis mixture, or from theproduct of methanol precipitation from a hot acetic acid solution.

Some surprising solvent mixtures are provided by the invention, in whicha polymerizable diacetylenic compound has a solubility which is markedlyhigher than its solubilities in either of the individual solvents. Theseand other newly discovered solubility options enable diacetyleniccompounds to be recrystallized in new ways, in some cases providing newreactivity choices.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

Some embodiments of the invention, and of making and using theinvention, as well as the best mode contemplated of carrying out theinvention, are described in detail herein, by way of example, withreference to the accompanying drawings, in which like referencecharacters designate like elements throughout the several views, and inwhich:

FIG. 1 is a simplified schematic diagram of one model of diacetylenepolymerization;

FIG. 2 is a skeletal drawing of a diacetylenic monomer molecule;

FIG. 3 shows a space-filling model of a diacetylenic monomer molecule;

FIG. 4 illustrates a solubility map wherein a number of solubilitypoints of solvents and solvent mixtures are shown;

FIG. 5 illustrates a further solubility map wherein a number ofsolubility regions are defined according to the invention;

FIG. 6 illustrates another solubility map wherein additional solubilityregions are defined according to the invention;

FIG. 7 illustrates an additional solubility map wherein still furthersolubility regions are defined according to the invention;

FIG. 8 illustrates another solubility map wherein further solubilityregions according to the invention are defined and a calculatedsolubility point for a diacetylenic monomer is shown;

FIG. 9 illustrates an embodiment of three-dimensional solubility mapuseful in the practice of the invention, in this case a Teas graph;

FIG. 10 is a bar chart showing the solubilities of a diacetylenicmonomer in various solvent systems at room temperature;

FIG. 11 shows two photomicrographs of two crystalline diacetylenicmonomers, that on the left being of a known diacetylenic monomer andthat on the right being of a diacetylenic monomer according to theinvention;

FIG. 12 is a graph showing the cumulative color-change response of anumber of diacetylenic monomers exposed to one ambient temperature;

FIG. 13 is a graph showing the cumulative color-change response of thediacetylenic monomers referenced in FIG. 12, exposed to another ambienttemperature;

FIG. 14 is a graph showing the cumulative color-change response of thediacetylenic monomers referenced in FIG. 12, exposed to a third ambienttemperature;

FIG. 15 is an X-ray diffraction pattern showing the results ofcharacterization of a first crystalline diacetylenic monomer;

FIG. 16 is a set of X-ray diffraction patterns showing the results ofcharacterization of a number of additional crystalline diacetylenicmonomers;

FIG. 17 shows two X-ray diffraction patterns showing the results ofcharacterization of two crystalline diacetylenic monomers precipitatedfrom diacetylenic solutions according to the invention;

FIG. 18 is a perspective view of a model of crystal structure for afirst diacetylenic monomer derivable from X-ray diffraction data;

FIG. 19 is a perspective view of a model of crystal structure for asecond diacetylenic monomer derivable from X-ray diffraction data; and

FIG. 20 shows schematically the orientation of crystal axes in relationto a crystal of a diacetylenic monomer.

Other examples of the practice of the invention will be or becomeapparent to a person of ordinary skill in the art in light of thisdisclosure.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides, inter alia, crystallized diacetyleniccompounds, sometimes referenced as “monomers” herein, crystalscomprising or consisting of diacetylenic compounds, also referenced as“diacetylenes” herein, and diacetylenic compositions which have newreactivities, or which provide more reactivity choices. In general, thediacetylenic materials provided by the invention can be prepared byphysical processing, or physical modification, of known diacetyleniccompounds without chemical change or modification of the startingmaterial, or changing the chemical structure of the starting material.

To facilitate physical processing and reactivity modification theinvention also provides new solvents and solvent systems fordiacetylenic monomers including solvents in which one or morediacetylenic monomers has good room-temperature solubility. Theinvention includes solutions of diacetylenic monomers dissolved in thenew solvents.

Also the invention provides quantitative information regardingdiacetylenic monomer solubility in such new solvents. Other aspects ofthe invention provide new diacetylenic monomer crystals and crystalstructure information which can be derived by recrystallization from thenew diacetylenic monomer solutions.

The invention includes methods of preparing solvent systems, methods ofrecrystallization, methods of determining useful crystal structureinformation as well as diacetylenic indicator solutions and molecularmodeling methods.

The invention includes a diacetylenic compound crystallized from thediacetylenic solutions described herein or prepared by a method asdescribed herein. The invention also includes a mixture of diacetyleniccompounds crystallized from the diacetylenic solution wherein themixture comprises a crystal phase and wherein the crystal phasecomprises two or more diacetylenic compounds.

The invention further includes methods of making an environmentalcondition indicator comprising applying the diacetylenic solution to asubstrate.

Many solvents have been suggested as being useful for dissolvingdiacetylenes in general. However, little solubility data exists as tothe particular solubility of a given diacetylenic compound in a specificsolvent. While some diacetylenic compounds may show some solubility in asuggested solvent, the solubility may be quite low and less than wouldbe useful for further processing. Many diacetylenic compounds havelittle known solubility at room temperature and may be processed atelevated temperatures. For example, some diacetylenic monomers arerecrystallized from hot glacial acetic acid at temperatures of the orderof 90-100° C.

Diacetylenic compounds for monitoring thermally unstable perishables aregenerally expensive to make and store. Room-temperature reactivediacetylenic compounds, which are useful for a number of purposesincluding freshness indicators, are expensive to store, sometimesrequiring refrigeration at low temperatures. These and otherconsiderations make it difficult to conduct large-scale screening teststo identify potentially useful new solubility properties of diacetyleniccompounds.

Accordingly, the invention provides a method of identifying prospectivesolvents, having useful diacetylenic solubility, which can reduce oravoid the need for wholesale screening of solvents. In some embodiments,the methods enable a specific solubility, for example at least 1 percentor at least 4 percent by weight of the solution, to be provided.

The present invention employs new understandings and insights regardingcertain diacetylenic compounds, or monomers, and provides means tomanipulate their indicator-related reactivity, and other properties,through changes in physical processing which leave the compoundsunchanged chemically. The invention includes embodiments which canprovide new reactivity characteristics without modifying thediacetylenic monomer via chemical reactions. This is because newmolecules that are chemically differentiated from established commercialproducts could require expensive studies for safety and other purposesfor some applications. Accordingly, the invention provides, in someaspects, crystallized diacetylenic compounds in new or modified physicalstates which have new or modified reactivities as compared withcompounds of chemically identical structure. For example, thediacetylenic compounds may have a particular crystal structure.

To lead to new reactivities or other properties it would be desirable tomore fully understand the structure of diacetylenic monomers and theirmechanisms of reaction at the molecular level. The invention alsoprovides new methods and products helpful to these ends.

While the invention is not limited by any particular theory, in thesolid state polymerization of a diacetylenic compound, a “monomer” or“diacetylenic monomer” in the context of polymerization, it is believedto be the crystal structure of the monomer which holds the individualdiacetylenic monomer molecules juxtaposed in a manner enablingspontaneous polymerization. This concept is illustrated in FIG. 1 wherethree diacetylenic monomer molecules are shown arrayed in parallelalignment, in a longitudinally and angularly ordered manner, as theymight be disposed in a solid crystal of the diacetylenic monomer. Theacetylenic groups of adjacent molecules are in sufficient proximity thatthey can spontaneously form double bonds between adjacent molecules tolink the monomer molecules together into the 1-4 addition polymerproduct.

More detailed models of two diacetylenic compounds are shown in FIGS. 2and 3. FIG. 2 illustrates the skeletal structure of2,4-hexadiyn-1,6-bis(ethylurea) monomer molecule and FIG. 3 illustratesspace-filling models of 2,4-hexadiyn-1,6-bis(ethylurea), upper model,and 2,4-hexadiyn-1,6-bis(propylurea), lower model.

These models of the mechanism of action of diacetylenic monomerpolymerization are believed accurate, but are probably notcomprehensive, i.e. other mechanisms may also come into play.Furthermore, they are insufficiently detailed for predictive modelingthat could help identify compounds, processing conditions, additives, orother modifications that would provide new diacetylenic monomers withnew indicator-related reactivities or reactivity profiles.

For example, it would be desirable to have more crystallographic andother information regarding unit cell dimensions and angles, atomicspacing and conformation in both the diacetylenic monomer and thecorresponding polymer.

Useful such information might be provided by X-ray crystallographicdata. However, little X-ray crystallographic data is believed availableowing to the difficulty of providing crystals of a reactive diacetylenicmonomer of sufficient size for comprehensive X-ray crystallographicstudies. Accordingly, for these and other purposes, it would bedesirable to provide relatively large crystals of a diacetylenicmonomer, for example crystals having a dimension of at least about 0.2mm.

While the invention is not limited by any particular theory, the way inwhich diacetylenic molecules pack together in crystals is understood torelate to the polymerizability of crystallites used for time-temperatureindicators. For these relatively complex molecules, it is believed notpresently possible reliably to predict crystal structure from knowledgeof the monomer structure alone. Hence, as stated, the discovery of a newcrystal phase for a given diacetylene monomer offers the potential tosignificantly expand the commercial applications opportunities for agiven diacetylenic monomer by providing a new set of time-temperatureparameters for reaction and correspondingly increased ability to closelymatch the time-temperature characteristics for the degradation ofperishable products or the desired degree of maturation for maturingproducts.

Some embodiments of the invention comprise methods of altering ormodifying the reactivity of a known or newly identified or newlysynthesized diacetylenic monomer. The reactivity modification method canbe a method of crystallizing, or recrystallizing, the diacetylenicmonomer from solution, which method comprises controlling at least onecrystallization parameter such as particle size, particle morphology,crystal structure, crystal defects, solvent molecules included in thecrystal and thermal history to obtain a diacetylenic monomer having atuned time-temperature dependence of color response.

While the invention is not limited by any particular theory, it is knownthat the polymerization reaction providing the color change that makesdiacetylenic monomers useful in ambient condition indicators isdirected, or influenced, by the diacetylenic monomer's crystalstructure. It is contemplated that in crystals of polymerizablediacetylenic monomer, the stacked diacetylenic monomer moleculescomprising the crystal are largely arranged in a lattice that canaccommodate the transition from monomer to polymer with only smalldimensional changes occurring between adjacent aligned monomer moleculesin the synthesis of the polymer molecule. It is also contemplated thatthe necessary small dimensional changes may occur more readily atcrystal surfaces and at crystal structural defects where diacetylenicmonomer molecules in the lattice have more freedom to move. Theseconsiderations are believed helpful to understanding certain aspects ofthe invention described herein which relate to altering or modifying thereactivity of a diacetylenic monomer by controlling a crystallizationparameter, such as one of the crystallization parameters describedherein.

In order to crystallize or recrystallize a diacetylenic monomer fromsolution it is necessary to provide a suitable solvent system for thediacetylenic monomer. As the term is used herein a “solvent system” cancomprise one or more solvents. Desirably, the solvent system is one thatdissolves the diacetylenic monomer at a useful loading, at an acceptabletemperature, and which does not react with the diacetylenic monomerunder the recrystallization conditions. When recrystallizing dissolveddiacetylenic monomers powders from heated supersaturated solutions ofthe diacetylenic monomers care is desirable to avoid undesiredpolymerization which is driven by temperature and time. For this reason,difficulty can occur, in some cases, in attempting to grow largecrystals, for example crystals having a dimension greater than 2 mm, ofpure diacetylenic monomer, from a supersaturated solution of thediacetylenic monomer, if this requires heating over extended periods oftime. Difficulty can also occur, in some cases, in attempting to growlarge crystals from a saturated room temperature, or colder, solutionowing to limited solubility of the diacetylenic monomer at thesetemperatures.

Additionally, the cost of processing a diacetylene monomer or mixture ofmonomers into printed indicator devices can be reduced by the discoveryof solvents that are capable of dissolving an adequate concentration ofdiacetylenic monomer or mixture of monomers. Moreover, diacetylenicmonomers are sometimes conveniently precrystallized before formulationas an ink which can be printed, for which purpose the availability of achoice of solvents providing good solubility can be desirable.

Accordingly, it would be useful to identify one or more solvent systemsthat can ameliorate one or more of these problems.

Solvent Mapping

Generally stated, the invention comprises, in one aspect, a method ofpreparing a solvent system for dissolving a diacetylenic compound whichcomprises providing a solvent map plotting the polar solubilityparameters of a number of prospective solvents for the diacetyleniccompound against the hydrogen bond solubility parameters of theprospective solvents to provide a solubility parameter point for eachprospective solvent. In addition the method includes identifying asolubility region for the diacetylenic compound from informationregarding the solubility of the diacetylenic compound in at least threeliquids, the diacetylenic compound not being insoluble in any one of theliquids. Desirably, the solubility region is a contiguous area of polarand hydrogen bond solubility parameters associated with desired solutionproperties. The method further includes selecting and employing in thesolvent system either a prospective individual solvent having asolubility parameter point lying within the solubility region and notbeing one of the liquids providing information regarding the solubilityof the diacetylenic compound, or a combination of prospective solventshaving a combination solubility parameter point lying within thesolubility region. The method of preparing a solvent system can, ifdesired, include mixing the prospective solvent or prospective solvents

Pursuant to the invention it has been determined that the solubility ofa diacetylenic monomer can be described in terms of thermodynamicproperties, for example solubility parameters such as those described byCharles Hansen and known as Hansen's solubility parameters. Hansendescribed three different solubility parameters which relate to threedifferent types of interaction between the solvent molecules, adispersive parameter, δ_(d), a polar parameter, δ_(p), and a hydrogenbonding parameter, δ_(h). The solubility parameters are measured inunits of the square root of megapascals, MPa^(1/2).

The three solubility parameters can be represented as the co-ordinatesfor a solubility point on a chart plotted in three dimensions, one foreach parameter. According to the Hansen theory, the closer two moleculesare to each other in this three dimensional space, the more likely theyare to dissolve into each other. Solubility parameters for many solventscan be found in, for example, “Hansen Solubility Parameters: A user'shandbook”, C. M. Hansen, 2000, CRC Press, ISBN 0-8493-1525-5. Alsoprovided is a method for estimation of solubility parameters that arenot tabulated in the reference.

While they may be useful in some circumstances, a number of limitationsare usually applicable. For example, the parameters are anapproximation, bonding between molecules is more subtle than the threeparameters might suggest. Molecular shape and size can be relevant ascan be other types of bonding such as induced dipole, van der Waals andelectrostatic interactions. Accordingly, it can be desirable toexperimentally verify solubility predictions derived from the use ofHansen solubility parameters.

Also, the Hansen solubility parameters are generally unknown fordiacetylenic monomers. Although Hansen solubility parameters cansometimes be calculated for relatively simple compounds, the two triplebonds present in diacetylenic compounds, and other factors, canintroduce uncertainties into the calculations so that reliable figurescannot be calculated for some diacetylenic monomers.

One embodiment of the present invention comprises a method ofidentifying a new solvent system for a particular diacetylenic monomerwhich utilizes Hansen solubility parameters but does not requireknowledge of the solubility parameters of the intended solute, thediacetylenic monomer. The invention includes solutions of thediacetylenic monomer in the newly identified solvent or solvents.

For example, solubility experiments can be conducted to determine orverify the solubilities of the diacetylenic monomer of interest in anumber of known solvents. The results of these solubility experimentscan be graphically represented or mapped or otherwise logicallyidentified, on a chart or map of some or all of the Hansen solubilityparameters for a group of solvents. The solvent map data can then beused to identify other solvents for the diacetylenic monomer by defininga region on the map of solubility parameter coordinates which can beexpected to correspond with enhanced diacetylenic monomer solubility.

The Hansen solubility parameters can be provided for a body of solventscomprising: known solvents for the diacetylenic monomer of interest inwhich the diacetylenic monomer has a known solubility; nonsolvents inwhich the diacetylenic monomer is known to have little or no solubility;and prospective solvents in which the solubility of the diacetylenicmonomer is unknown.

Any suitable number of known solvents can be employed to provide dataregarding the solubility of the diacetylenic monomer and help define asolubility region for the diacetylenic monomer. Some embodiments of theinvention employ data from two or three known solvents. Otherembodiments employ data from four or five or more known solvents. Forexample, the information used to identify the solubility region cancomprise information about the solubility of the diacetylenic compoundin at least five liquids selected from the group consisting of alcohols,acids, water, aromatic compounds, nitrogen-containing compounds, esters,glycols, halogenated organic compounds, alkanes, and mixtures of theforegoing liquids.

The number of known solvents whose solubility data is employed can befrom 2 to about 20 or more. Solubility data for a relatively smallnumber of solvents, for example from about 3 to about 10, are employedin some embodiments of the invention.

If desired, solubility data from a larger number of solvents can beemployed. Desirably, but not essentially, solvents having parameters indifferent parts of the chart can be employed. When a region of probablepeak solubility has been identified, if desired, additional data fromsolvents on opposite sides of the region identified, can be employed.For example additional solvents can be selected that have solubilityparameters such that a straight line from the solvent's solubility pointto the solubility point of another solvent passes through the region ofprobable peak solubility.

The solvent map can comprise a number of solubility points for each ofthe known solvents plotted against the solubility parameters. Eachsolubility point is defined by coordinates of the respective solubilityparameters in three-dimensional space. For simplicity, some embodimentsof the invention can utilize data for two of the three parameters, forexample, the polar parameter and the hydrogen bonding parameter, so thatthe solubility points can be mapped in two-dimensional space. Thesolvent map can have two or three axes defining the space in which thesolubility points are plotted according to whether two or all threeHansen parameters are employed.

In one embodiment of the invention, known solubility points are plottedagainst the hydrogen bonding parameter and the polar parameter, with thehydrogen bonding parameter arbitrarily being on the y-axis and the polarparameter can being on the x-axis. In this embodiment of the invention,for simplicity, the dispersion parameter is ignored or consideredempirically. If desired, the dispersion parameter can be considered inconnection with some, but not all solvents, as will be explained herein.

In another embodiment of the invention, the dispersion parameter isplotted in a third dimension, on a z-axis, or in another suitablemanner, and the method is extended into the third dimension, as will beapparent to a person of ordinary skill in the art in light of thisdisclosure. Other embodiments of the invention employ either polarparameter data or hydrogen parameter data, together with dispersionparameter data, in a two-dimensional solvent map.

In the solvent map, solvents in which the diacetylenic monomer is knownto have a desired solubility can be marked, colored, labeled orotherwise graphically or logically identified, in the solvent map, todistinguish the known solvents from known nonsolvents in the solventmap. The solvent map can be specific to the particular diacetylenicmonomer. The desired solubility can have any desired value: for example,a solubility in the range of from about 0.1 percent to about 20 percent.Some embodiments of the invention employ desired solubilities of about0.5, 1, 4, 7, 10 and 13 percent, respectively. Solvents providing atleast the desired solubility can be marked while solvents known toprovide a lower solubility, or in which the particular monomer isinsoluble, are not marked or are marked differently.

Solubilities expressed in percentages herein are to be understood asbeing by weight of the solute based on the weight of the solution.Solubilities can be heated solubilities or room temperaturesolubilities, as noted herein or as will be apparent from the context.

Thus known solvents and known nonsolvents exhibiting a desiredsolubility or lack thereof for a particular diacetylenic monomer can beidentified. From this information, a solubility region embracingcombinations of solubility parameters providing enhanced solubility forthe diacetylenic monomer can be defined or indicated on the solubilitymap. The defined solubility region can also embrace the solvent map areabetween the embraced known solvent points. Optionally, the definedsolubility region can also embrace an area or areas adjacent to orcontiguous with the known solvent points.

The solubility region for the diacetylenic monomer can be identifiedfrom information regarding the solubility of the diacetylenic monomer inat least three liquids in which the diacetylenic monomer is notinsoluble. Any suitable number of liquids can be employed according tothe solubility information available, for example five, ten or twenty ormore liquids.

Usefully, the solubility region can be a contiguous area of polar andhydrogen bond solubility parameters associated with desired solutionproperties. Also, the defined solubility region can embrace combinationsof Hansen parameter values that are associated with the desiredsolubility. Desirably, the defined solubility region includes all ormost of the known solvents providing the desired solubility for theparticular diacetylenic monomer. Desirably also, the defined solubilityregion excludes all or most of the nonsolvents being solvents that donot provide that desired solubility.

If desired the defined solubility region can be bounded by a perimeterline. The perimeter line could be an open shape for example a “V” or a“C” but desirably is a closed loop. Depending upon the solubility dataappearing in the solvent map, the closed loop perimeter line can have anirregular or a regular or geometric shape, for example, the shape of anellipse, oval, circle, triangle, rectangle, polygon, quadrilateral orother suitable shape.

Also, if desired, the perimeter line can be positioned and shapedstochastically, with the assistance of mathematical analysis, to definethe line according to probabilities that the combinations of Hansenparameters embraced in the defined solubility region will be possessedby solvents having, or not having, the desired solubility properties.Alternatively, the perimeter line can be determined empirically, forexample by eye.

If desired, the solubility region can be defined to embrace combinationsof solubility parameters that are expected to provide a certain minimumsolubility of the diacetylenic monomer, for example, about 1 percent,about 4 percent, about 7 percent or about 10 percent solubility byweight based on the weight of the solution.

Such a solubility region can be helpful in providing diacetylenicsolutions comprising a minimum proportion of diacetylenic compoundselected from the group consisting of at least about 1, at least about 7and at least about 10 percent by weight of the diacetylenic compound,based upon the weight of the diacetylenic solution. If desired, thediacetylenic solutions can have still higher concentrations of thedissolved diacetylenic compound or compounds.

In some embodiments of the invention the solubility region is defined ormodified according to other factors in addition to solubilityparameters. For example a solubility region can be positioned or shapedto avoid solvents or solvent combinations which have too low a boilingpoint to provide a desired solubility. Also, the solubility region canbe positioned or shaped to include or exclude a solvent or solventsystem having particular structural features affecting its solvatingpower for a particular solute that may not be reflected in its Hansensolubility parameters. For example, a solvent having basic characterwith one or more electron donor groups may have surprising solvatingpower for a solute having one or more available electron acceptor groupssuch as the positive end of a dipole whose negative end is lessaccessible to a potential solvent. However, the invention is not to belimited by any such theory.

Prospective solvents and solvent systems providing, or likely to providethe desired solubility for the diacetylenic monomer can be identified byseeking other solvent systems having solubility points in the definedsolubility region.

Surprisingly, it has been found that some useful solvent systems for adiacetylenic monomer can be identified employing a solubility map ofhydrogen bonding and polar parameters, without employing the dispersionparameter. The invention includes embodiments wherein the dispersionparameter is ignored.

Some embodiments of the invention comprise solutions of the diacetylenicmonomer in a solvent having a solubility parameter point lying in thedefined solubility region. Further embodiments of the invention comprisesolutions of the diacetylenic monomer in solvent systems having asolubility parameter point in the defined solubility region.

When miscible solvents are combined, their Hansen parameters can becombined by averaging the Hanson parameters for the liquids in themixture using weighting factors that are the volume fraction of eachliquid in the mixture. Thus, on a solvent map the solubility point for amixture of two solvents will usually be on a straight line between theindividual solubility points, at a distance along the line inverselyproportional to their respective volume fractions in the mixture.Alternatively, if desired they can be combined by ratio in terms of therespective mass fraction of each solvent in the mixture.

Desirably, the two component solvents of a two-component solvent systemcan have individual solubility points so positioned on the solvent mapthat a straight line between them passes through the defined solubilityregion. The proportion of the solvents in the mixture can be selected oradjusted so that the solubility point of the mixture lies in the definedsolubility region.

Some further embodiments of the invention comprise solvent systemshaving three, four or more components that are miscible with each otherand do not react with one another or with the solute. If desired, thesolvents can be selected so that the solvent system has a solubilitypoint in a desired solubility region by calculating the parameters ofthe solubility point to be equal to the average Hansen parametersweighted by the volume fraction of each constituent solvent.

Some exemplary solvent systems include individual solvents as well asmixtures of two or more solvents. Some embodiments of useful solventsystem comprise at least one component solvent which is a poor solventor a nonsolvent for the diacetylenic compound or compounds to bedissolved. The solvents in a mixture to be employed in the practice ofthe invention desirably can be completely miscible one with the other.

One solvent system useful in the practice of the invention comprises twopoor but miscible solvents or nonsolvents for the diacetylenic compoundor compounds, for example ethyl alcohol and water. Another usefulsolvent system comprises one or more relatively good solvents for thediacetylenic monomer or monomers, for example a solvent or solventscapable of dissolving at least 1 percent by weight of the diacetylenicmonomer, mixed with one or more poor solvents or nonsolvents for thediacetylenic compound or compounds.

To prepare a solvent map to identify prospective new solvents for adiacetylenic monomer, some information as to the solubility of thediacetylenic monomer in a number of solvents is required, as describedherein. If adequate solubility information is not available in the art,solubility tests can be performed.

Prospective solvents and solvent systems can be selected for testingaccording to available solubility information for the diacetylenicmonomer concerned. Solubility points for each of the selected solventsand solvent systems can be mapped on a plot of hydrogen bonding (δH), onthe Y-axis, versus polar parameters (δP), on the X-axis or as otherwisedescribed or suggested herein.

If the polar and hydrogen bonding solubility parameters of thediacetylenic monomer are known or can be calculated with confidence, asolubility point for the diacetylenic monomer can also be mapped. Atrial solubility region can then be mapped in relation to thediacetylenic monomer solubility point and tested experimentally.

In cases where the polar and hydrogen bonding solubility parameters ofthe diacetylenic monomer are unknown and cannot be calculated withconfidence, a solubility region can be determined from the results ofexperiments, for example as is illustratively described in Example 1below. Elevated temperatures can be employed for diacetylenic monomersthat display limited solubility properties at room temperature. Forexample, process temperatures in the range of from about 90 to about 95°C. have been employed for recrystallizing a diacetylenic monomer from anacetic acid solution. Generally, temperatures in a range of about 50 to100° C., or within other suitable limits, can be employed according tothe boiling point of the solvents utilized, the stability of thediacetylenic monomer dissolved, the potential for undesiredpolymerization and other factors.

In this specification, where a solubility is stated without reference toa temperature, the temperature is to be understood as being anytemperature reasonably attainable with the solvent in question, atstandard atmospheric pressure, i.e. up to a few degrees Celsius abovethe boiling point of the solvent, for example not more than 5° C.higher.

Some nonlimiting examples of the practice of the invention will now bedescribed.

Example 1 Solubility Tests and Definition of a Solubility Region

This example illustrates solvent mapping, testing and solubility regiondefinition for a diacetylenic monomer for which new solvents andsolubility information are desired, namely2,4-hexadiyn-1,6-bis(ethylurea) and for which reliable solubilityparameter information is not available. In this example, solubilitypoints are mapped for each of a number of representative samples of awide range of solvents of different chemical types and physicochemicalcharacteristics, according to their solubility parameters. Thesolubility points of the representative solvents (filled squares) aremapped on a plot of hydrogen bonding (δH), on the Y-axis, versus polarparameters (δP), on the X-axis, generating a map such as that shown inFIG. 4. Also shown in FIG. 4 are solubility points for solvent systemscomprising 25 percent by weight water/solvent mixtures (unfilledsquares). These mixtures are suggested as potentially useful solventsystems for dissolving 2,4-hexadiyn-1,6-bis(ethylurea) by applyingsolubility test results for individual solvents (described below) to theFIG. 4 map of their solubility parameters.

Each solvent is tested for its ability to dissolve at least 1 percent byweight 2,4-hexadiyn-1,6-bis(ethylurea) at a temperature not more than 5°C. above the boiling point of the solvent. Because the boiling points ofthe solvents tested vary widely, ranging from 56° C. to 189° C. thesolvents are processed in batches at temperatures of 60, 75, 82, and 90°C., respectively. The process temperature desirably is not greater than4 to 5° C. above a given solvent's boiling point.

Without solubility information regarding the diacetylenic monomer underconsideration, or knowledge of its solubility parameters, it is notfeasible to identify in FIG. 4 a region of possible enhanced solubilityof the diacetylenic monomer.

Some exemplary solubility data obtainable for2,4-hexadiyn-1,6-bis(ethylurea) from the above-described solubility testwith the solvents indicated, are set forth in Table 1 below along withsolubility parameter information for the solvents. Also included inTable 1 are data regarding the 25 percent by weight water/solventmixtures.

TABLE 1 Solubility Parameters and 1% Solubility Results SolventDispersive Polar Hydrogen Boil T Process T KE soluble name parameterparameter parameter (° C.) (° C.) at 1% wt? Acetone 15.5 10.4 7.0 56 60No Chloroform 17.8 3.1 5.7 61 60 No 25% Water/Acetone 15.5 11.8 15.8 6160 Yes Methanol 15.1 12.3 22.3 65 60 Yes THF 16.8 5.7 8.0 66 60 Non-Hexane 14.9 0.0 0.0 69 75 No Ethyl acetate 15.8 5.3 7.2 77 75 NoAcrylonitrile 16.5 17.4 6.8 77 75 No Ethanol 15.8 8.8 19.4 78 75 YesBenzene 18.4 0.0 2.0 80 75 No Cyclohexane 16.8 0.0 0.2 81 82 No 25%Water/IPA 15.7 8.6 22.9 81 82 Yes Acetonitrile 15.3 18.0 6.1 82 82 No2-Propanol (IPA) 15.8 6.1 16.4 82 82 Yes 25% Water/Ethanol 15.7 10.625.2 83 82 Yes 1-Propanol 16.0 6.8 17.4 97 82 Yes Water 15.5 16.0 42.4100 90 No 25% Water/formic acid 14.6 12.9 23.1 100 90 Yes Formic acid14.3 11.9 16.6 101 90 Yes Toluene 18.0 1.4 2.0 111 90 No 25%Water/acetic acid 14.8 10.0 20.7 113 90 Yes Pyridine 19.0 8.8 5.9 115 90Sparingly Acetic acid 14.5 8.0 13.5 118 90 Yes 25% Water/DMF 16.9 14.319.1 140 90 Yes DMF 17.4 13.7 11.3 153 90 Yes Cellosolve ® acetate 16.04.7 10.6 156 90 No E3EP 16.1 3.3 8.8 166 90 No 25% Water/DMSO 17.7 16.318.3 167 90 Yes 1,2-Dichlorobenzene 19.2 6.3 3.3 179 90 No Glycerol 17.412.1 29.3 182 90 No DMSO 18.4 16.4 10.2 189 90 Yes Ethylene glycol 17.011.0 26.0 197 90 Yes Average 16.4 9.1 13.9 +/− Std. deviation 1.3 5.29.5

As used in Table 1, and elsewhere herein, “DMF” indicates dimethylformamide, “DMSO” indicates dimethyl sulfoxide, “E3EP” indicates ethyl3-ethoxypropionate” and “THF” indicates tetrahydrofuran.

The results for the individual solvents in Table 1 indicate five thatdissolve at least 1 percent by weight of 2,4-hexadiyn-1,6-bis(ethylurea)and could accordingly warrant further study. These solvents are dimethylsulfoxide (DMSO), acetic acid, N,N-dimethyl formamide (DMF), ethanol(EtOH), and ethylene glycol. As expected, following use of thesolubility map, the water/solvent mixtures all dissolve at least 1percent by weight of 2,4-hexadiyn-1,6-bis(ethylurea).

Applying the Table 1 results from the 1 percent weight solubility teston the map of Hansen solubility parameters enables a distinct region onthe map to be defined, in terms of polar and hydrogen bonding parameterswhere 2,4-hexadiyn-1,6-bis(ethylurea) is soluble at reasonableprocessing temperatures. This can be done without having informationregarding a solubility point and values for the solubility parameters ofthe solute, 2,4-hexadiyn-1,6-bis(ethylurea).

Example 2 Further Solubility Tests

The Example 1 solubility tests are then repeated for different soluteconcentrations, in this case 4 percent, 7 percent, and 10 percent byweight of 2,4-hexadiyn-1,6-bis(ethylurea) in each of the solventsdemonstrating at least 1 percent solubility in the previous test as wellas the water/solvent mixtures. A 90° C. water bath is employed tomaintain the solvent or solution temperature and results obtainable aretabulated in Table 2 below, solubility parameter information again beingincluded to facilitate understanding of the data for acetone and water,for reference.

TABLE 2 Solubility Trial Results at Various Solubilities Polar HydrogenBoil Solvent parameter parameter Temp Is KE soluble at name (MPa^(1/2))(MPa^(1/2)) (° C.) 1%? 4%? 7%? 10%? Acetone 10.4 7.0 56 No No No No 25%Water/ 11.8 15.8 61 Yes Yes No No Acetone Methanol 12.3 22.3 65 Yes YesNo No Ethanol 8.8 19.4 78 Yes No No No 25% Water/ 8.6 22.9 81 Yes No NoNo IPA 2-Propanol 6.1 16.4 82 Yes No No No (IPA) 25% Water/ 10.6 25.2 83Yes Yes No No Ethanol 1-Propanol 6.8 17.4 97 Yes No No No Water 16.042.4 100 No No No No 25% water/ 12.9 23.1 100 Yes Yes Yes No formic acidFormic acid 11.9 16.6 101 Yes Yes Yes Yes 25% water/ 10.0 20.7 113 YesYes Yes No acetic acid Pyridine 8.8 5.9 115 Yes No No No Acetic acid 8.013.5 118 Yes Yes Yes Yes 25% Water/ 14.3 19.1 140 Yes Yes Yes No DMF DMF13.7 11.3 153 Yes Yes Yes Yes 25% Water/ 16.3 18.3 167 Yes Yes No NoDMSO DMSO 16.4 10.2 189 Yes Yes Yes Yes Ethylene 11.0 26.0 197 Yes No NoNo Glycol

These results demonstrate the practice of various aspects of theinvention. For example, two new solvents for2,4-hexadiyn-1,6-bis(ethylurea) providing solubilities in excess of 10percent are identified, namely formic acid and dimethyl sulfoxide.Formic acid can solvate nearly 13% 2,4-hexadiyn-1,6-bis(ethylurea) byweight at room temperature.

Also, it can be noted that two non-solvents for2,4-hexadiyn-1,6-bis(ethylurea), namely water and acetone, can becombined together, combining their solubility parameters, to provide asolvent system in which 2,4-hexadiyn-1,6-bis(ethylurea) has anunexpectedly good solubility of at least 4 percent by weight.

Furthermore, surprisingly, a 25% water/ethanol mixture (1 part by weightwater combined with 3 pars by weight ethanol) provides a better2,4-hexadiyn-1,6-bis(ethylurea) solubility, at least 4 percent byweight, than does pure ethanol for which the2,4-hexadiyn-1,6-bis(ethylurea) solubility is less than 4 percent byweight, notwithstanding the fact that 2,4-hexadiyn-1,6-bis(ethylurea) isinsoluble in water.

Careful consideration of such findings suggests one or more regions ofenhanced or optimal 2,4-hexadiyn-1,6-bis(ethylurea) solubility lyingwithin a narrow range of solubility parameters. Diacetylenic monomersolution embodiments and other embodiments of the invention can employone or more combinations of solvents that are completely miscible andhave solubility parameters that can be combined to lie in such anenhanced or optimal solubility region for the particular diacetylenicmonomer.

Several ways of applying some of the 2,4-hexadiyn-1,6-bis(ethylurea)solubility results shown in Table 2 to a solubility map such as is shownin FIG. 4, are illustrated in FIG. 5.

Referring to FIG. 5, the parameter quantifying a solvent's dipolestrength, the polar parameter, sometimes referenced “δP”, is plottedalong the X-axis and the parameter quantifying the solvent'shydrogen-bonding strength, the hydrogen bonding parameter, sometimesreferenced “δH”, is plotted along the Y-axis. The units in each case aremegapascals^(1/2), MPa^(1/2). In this embodiment of the invention, thedispersion parameter, sometimes referenced “δP”, is not employed.

In FIG. 5, dark squares indicate solvents providing at least 10 percentsolubility, intermediate shaded squares indicate solvents providing atleast 4 percent solubility and light squares indicate solvents providingat least 1 percent solubility. “X” indicates a solvent in which2,4-hexadiyn-1,6-bis(ethylurea) is insoluble or has less than 1 percentsolubility. For clarity, most of the solvent names were omitted exceptfor water, acetone and solvents able to dissolve 10% weight2,4-hexadiyn-1,6-bis(ethylurea).

Three solubility regions having the approximate solubility parametersthat are apparently required for threshold solubilities of 1 percent, 4percent, and 10 percent respectively are shown in FIG. 5. The solubilityregions are overlaid one on the other with the largest solubility regionembracing solvent systems providing at least 1 percent2,4-hexadiyn-1,6-bis(ethylurea) solubility. A smaller region within thislarge region provides at least 4 percent 2,4-hexadiyn-1,6-bis(ethylurea)solubility and the smallest region, which lies wholly within thissmaller region, provides at least 4 percent2,4-hexadiyn-1,6-bis(ethylurea) solubility. As defined in FIG. 5, eachsolubility region has a trapezoidal shape. However, the solubilityregions can have other shapes.

While the invention is not to be limited by any particular theory, it iscontemplated that the low boiling point of acetone may not allow thesolution to become hot enough to attain the solubilities for2,4-hexadiyn-1,6-bis(ethylurea) displayed by the other four solvents inthe smallest solubility region, all of which have boiling points of over100° C.

With the assistance of a solubility map such as that shown in FIG. 5,various practical guidelines for identifying useful solvents can bedetermined, according to solubility needs. For example, to dissolve atleast about 1 percent by weight of 2,4-hexadiyn-1,6-bis(ethylurea), asolvent system having a polar solubility parameter in the range of fromabout 7.5 to about 16.6 MPa^(1/2) and a hydrogen bonding parameter inthe range of from about 8.5 to about 26.0 MPa^(1/2) can be employed. Todissolve at least about 4 percent by weight of2,4-hexadiyn-1,6-bis(ethylurea), a solvent system having a polarsolubility parameter in the range of from about 7.7 to about 16.5MPa^(1/2) and a hydrogen bonding parameter in the range of from about9.0 to about 22.5 MPa^(1/2) can be employed. To dissolve at least about10 percent by weight of 2,4-hexadiyn-1,6-bis(ethylurea), a solventsystem having a polar solubility parameter in the range of from about8.0 to about 16.4 MPa^(1/2) and a hydrogen bonding parameter in therange of from about 10.0 to about 17.0 MPa^(1/2) can be employed.

Thus, data such as is shown in Table 2 can be used to identify regionsof desirable solubility on a solubility map of the solvent solubilityparameters. The solubility map can, in turn, be used to identify one ormore new solvent systems for the diacetylenic monomer of interest.

The example of a two-dimensional solvent map depicted in FIG. 6 showsthe solubility points for a number of solvents and a number of definedsolubility regions illustrative of what can be empirically determinedfrom solubility tests on the solubility of a diacetylenic monomer suchas 2,4-hexadiyn-1,6-bis(ethylurea) in selected solvents systems.

FIG. 6 is generally similar to FIG. 5, with the difference that in FIG.6 instead of the trapezoidal solubility regions defined in FIG. 5, twoelliptical solubility regions of different sizes are defined, thesmaller lying wholly within the larger and embracing solubility pointsthat are expected to provide higher solubilities for2,4-hexadiyn-1,6-bis(ethylurea). The larger ellipse is defined toembrace a range of solubility parameters expected to be appropriate forsolvents and solvent systems providing a minimum desired2,4-hexadiyn-1,6-bis(ethylurea) solubility. The smaller ellipse isdefined to embrace a range of solubility parameters expected to beappropriate for solvents and solvent systems providing a higher oroptimal desired 2,4-hexadiyn-1,6-bis(ethylurea) solubility. Also, thevarious solubility points are labeled with the solvent names.

The solubility region perimeter lines in FIGS. 5-7 can be determined byinterpolation from the known solubilities and from the new solubilitiesidentified in solubility tests such as described in Examples 1 and 2, orin other suitable manner.

FIG. 7 is generally similar to FIG. 6 with the difference thatsolubility points for the water/solvent mixtures shown in Table 2 areincluded and identified, while individual solvent solubility points,other than water, are not identified.

Referring to FIG. 7, it can be seen that water lies well outside theenhanced solubility regions shown consistently with its being, as statedabove, a non-solvent for the particular diacetylenic monomer tested,namely 2,4-hexadiyn-1,6-bis(ethylurea). Surprisingly, water can be mixedwith other solvents with which it is miscible to provide new solventsystems having good solubility for 2,4-hexadiyn-1,6-bis(ethylurea). Someof these mixtures are marked with triangles in FIG. 7. For example,2,4-hexadiyn-1,6-bis(ethylurea) has only limited solubility in acetonealone but has a useful solubility in an acetone-water mixture. Astraight line between the solubility points for acetone and water passesthrough the region of peak solubility for2,4-hexadiyn-1,6-bis(ethylurea). A mixture having a minor proportion ofwater, 25% in the test example herein, locates the mixture solubilitypoint in the peak solubility region.

The solubility map shown in FIG. 8 comprises solubility points for anumber of solvents listed by functional group, and for the individualsolvents water and tetrahydrofuran. The solubilities are determined intrials at temperatures up to 90° C. or near the boiling point of a givensolvent, as described in Example 1.

Using the data obtained, elliptical solubility regions are defined forsolubility coordinates correlated with solubilities of at least about 1%by weight, of at least about 4% by weight and of at least about 10% byweight of 2,4-hexadiyn-1,6-bis(ethylurea).

Also shown in FIG. 8 is an example of a calculated solubility point fora diacetylenic monomer, in this case 2,4-hexadiyn-1,6-bis(ethylurea),which is referenced “KE” in FIG. 8 and some other figures of theaccompanying drawings. The calculated solubility point, indicated by adark triangle in FIG. 8 is determined by calculation of its Hansensolubility parameters according to the method of van Krevelyn, with alisting of group increments. The calculated values, in MPa^(1/2), are:δD=20.8, δP=7.3, and δH=10.1. These calculated values appear to bereasonable, but do not agree well with experiment:2,4-hexadiyn-1,6-bis(ethylurea) (“KE”) falls outside of its own regionof solubility. One method of calculating Hansen solubility parametersaccording to the method of van Krevelyn is described by Brandrup, J.;Immergut, E. H.; Grul E. A., Eds. in Polymer Handbook, 4th ed.; JohnWiley & Sons, Inc.: Hoboken, N.J.; 1999; Vol. 2.

The solubility map shown in FIG. 9 is an embodiment of what is known asa Teas graph and it plots a third solubility parameter, the dispersionparameter, in addition to the polar and hydrogen bonding parametersplotted in FIGS. 5-8.

In order to plot all three solubility parameters on a single planargraph, an assumption is made that all materials have the same Hildebrandsolubility parameter. This is an approximation for convenience. AHildebrand value is the root mean square average of the three Hansenparameters which are often considered as additive components of theHildebrand value. Teas graph plots the relative contribution of each ofthe three component Hansen solubility parameters, (i.e. the dispersionparameter, polar parameter, and hydrogen bonding parameter) to the totalHildebrand value. Solubility parameters can then be expressed inproportions of a whole rather than unrelated parameters. A Teas graph isfurther described by John Burke in “Solubility Parameters: Theory andApplication” The Book and Paper Group Annual, Vol. 3, 1984 The AmericanInstitute for Conservation of Historic and Artistic Works (AIC).

Approximate solubility points for a variety of groups of solvents areshown in FIG. 9, namely, for carboxylic acids, polar aprotic solvents,glycols, alcohols, alkanes, aromatics, esters, halogenated solvents,ketones, nitriles, as well as for water, pyridine and tetrahydrofuran.

The solubility points for groups are approximate averages for the groupand possible variation of the solubility parameters with temperature isignored, as is the case with the other solubility maps shown.

Two solubility regions indicating zones of enhanced solubility for2,4-hexadiyn-1,6-bis(ethylurea) are shown, a broken line triangle,intended to correlate approximately with at least about 1% by weightsolubility and within that, a solid line triangle intended to correlateapproximately with at least about 10% be weight solubility. Theseregions can fit reasonably well with experimental results. One outlieris pyridine which solvates about 1% by weight2,4-hexadiyn-1,6-bis(ethylurea), but lies outside the plotted triangles.

Similar results are believed obtainable for2,4-hexadiyn-1,6-bis(propylurea) (also referenced herein as “KPr”) witha three-dimensional solubility map such as that shown in FIG. 9. Otherways of plotting three or more dimensions of solubility parameters willbe or become apparent to those skilled in the art.

For some purposes it would be useful to have a solvent which effectivelysolvates a diacetylenic monomer at room-temperature. Crystal growth canbe facilitated at lower temperatures, where polymerization is likely tobe less of a factor than at higher temperatures. Also, good roomtemperature solubility has potential value in downstream processing andmanufacturing applications of diacetylenic monomers. Accordingly, someembodiments of the invention include solutions of diacetylenic monomersin solvent systems capable of providing significant room-temperaturesolubility for a diacetylenic monomer.

For this or other purposes, room temperature solubilities of adiacetylenic monomer, 2,4-hexadiyn-1,6-bis(ethylurea) recrystallizedfrom acetic acid, in a variety of solvent systems can be determined, forexample as shown in Table 3, below. Table 3 shows solubilities at a roomtemperature of 20° C. in weight percent based on the weight of thesolution.

TABLE 3 Solubilities of 2,4-hexadiyn-1,6-bis(ethylurea) at 20° C.Solubility Solvent System (wt. % of the Solution) Methyl alcohol “MeOH”0.27 Ethyl alcohol 0.17 Isopropyl alcohol 0.09 Tetramethyl urea 0.90Formic acid 23 Acetic acid 0.6 Dichloroacetic acid 33Trifluoroaceticacetic acid 30 DMF 4 DMSO 4 Acetone/water 4:1 0.16Ethanol/water 4:1 0.18

1,1,3,3 tetramethyl urea, also called “tetramethyl urea” and sometimesreferenced “TMU” can dissolve up to 7% weight2,4-hexadiyn-1,6-bis(ethylurea) at a temperature of 90° C. in a closedvial.

Using information regarding solubilities of2,4-hexadiyn-1,6-bis(ethylurea), such as is shown in Table 3 below, roomtemperature solutions can be made up for recrystallization, for use asinks to prepare environmental condition indicators or for otherpurposes. Other diacetylenic monomers solutions can be similarlyprepared.

The bar chart shown in FIG. 10 depicts the room-temperature solubilitieslisted in Table 3 graphically.

As is the case elsewhere herein, the acetone/water and ethanol/watersolvent mixtures are given in weight-for-weight proportions in Table 3and FIG. 10. It can be seen from Table 3 and FIG. 10 that some of thesolvent systems displaying elevated solubility at higher temperatures,for example acetic acid and the several aqueous mixtures, have onlylimited solubility at room temperature.

In contrast, the halogenated solvents and formic acid display excellentroom temperature solubility. However, these solvents have well-knownhandling characteristics that may make them unsuitable for somepurposes. A useful aspect of the invention provides new solvent systemsfor one or more diacetylenic compounds which are environmentallyfriendly or compatible. An example of an environmentally compatiblesolvent system is an aqueous solvent system comprising a high proportionof water, for example more than 50 percent by weight water.

The solubilities of other diacetylenic monomers in the solvent systemsprovided by the invention or employed in the practice of the invention,can be determined by extrapolation or routine experimentation. Forexample, the solubility of 5,7-dodecadiyn-1,12-bis-n-octadecyl urethane(also “4DOD” herein) in various solvent systems can be determined asdescribed in Example 2A below.

5,7-dodecadiyn-1,12-bis-n-octadecyl urethane (“4DOD”) has the followingchemical structure

C₁₈H₃₇NHCOO(CH₂)₄CCCC(CH₂)₄COONHC₁₈H₃₇

and is radiation sensitive, exhibiting a color change, but relativelyinsensitive to normal ambient thermal conditions. 5,7-dodecadiyn-1,12diol bis(n-butoxycarbonyl urethane is another compound having which isradiation sensitive, but relatively insensitive to normal ambientthermal conditions. The invention includes radiation monitoring devicesemploying one or more such compounds to provide a visual indication ofcumulative exposure to high energy ambient radiation, for example,ultraviolet light, alpha rays, beta rays or other subatomic particlestreams, X-rays, gamma rays and/or the like.

Example 2A Solubility of 5,7-dodecadiyn-1,12-bis-n-octadecyl urethane(“4DOD”)

To serve as indicator agent, a thermally insensitive polymerizablediacetylenic monomer, namely 5,7-dodecadiyn-1,12 diol bis(n-octadecylurethane), “4DOD” hereinafter, is synthesized in sufficient quantity forpreparation of a master batch of ink, by the method described in YeeU.S. Pat. No. 4,215,208 at column 17, lines 47-65 and is stored in afreezer. A small quantity of 4DOD is taken from frozen storage and istested at room temperature for solubility in various solvent systemsemploying the following procedure.

100 g of deionized water is weighed into a 200 mL glass beaker. 4DODpowder is added to the glass beaker until the solution is saturatedallowing excess 4DOD to remain present as undissolved solid. 75 g ofdeionized water is weighed into another 200 mL glass beaker, and 25 gacetone is added. 4DOD is then added to the water-acetone solvent systemin the glass beaker until the solution is saturated and an excess of4DOD remains as undissolved solid. 75 g of deionized water is weighedinto a third 200 mL glass beaker. 25 g ethanol is added to the water andthen 4DOD is added to the water-ethanol mixture until the solution issaturated and an excess of 4DOD remains as undissolved solid. Eachsolution is stirred on a magnetic plate for 16 hours at a controlledroom temperature of about 25° C.

After 16 hours of stirring, 7 g of each solution (soluble portion only,avoiding any undissolved solid material) is transferred to a separatealuminum foil pan. The aluminum foil pans are left to stand under a fumehood for 2 hours to allow any volatile solvent to evaporate, and arethen dried in a vacuum oven for one 1 hour. Each aluminum foil pan isthen weighed and the solubility of the 4DOD in each solvent system iscalculated in terms of the percent of solute based on the weight of thesolvent system. Some results obtainable are shown in Table 2A below:

TABLE 2A Solubility Results for 4DOD Weight of Weight of Calculatedsolution Solute solubility of Solvents before drying after drying 4DOD(wt %) Water 7.0 g 0.00201 g 0.03% 75% Water 7.0 g 0.70618 g 10% 25%Acetone 75% Water 7.0 g 0.62184 g 9% 25% Ethanol 100% Ethanol 7.0 g2.58206  37% 100% Acetone 7.0 g 2.21616  32%

As can be seen from the results in Table 2A, under the test conditions,4DOD has minimal solubility in water. However, environmentallyacceptable solvent systems comprising a high proportion of water mixedwith ethanol or acetone show dramatically increased solubility of 4DODin water of about 9 or 10 percent by weight of the solvent system. Theresults also show a remarkably high solubility for 4DOD in theindividual organic solvent alone, ethanol or acetone.

The methods of the invention provide flexibility in designing solventsystems for a diacetylenic monomer, for example for2,4-hexadiyn-1,6-bis(ethylurea). Thus, the solvent maps shown in FIGS.5-7 are illustrative of solvent maps that can be employed to identifynew solvents for a diacetylenic monomer or to create new solvent systemsfor the diacetylenic monomer, or both. The new solvents and solventsystems can provide new solubility information regarding thediacetylenic monomer useful in the subsequent processing or utilizationof the diacetylenic monomer. The new solubility information can comprisenew knowledge regarding a solvent system in which the diacetylenicmonomer has useful solubility or new quantitative information regardingits solubility in a solvent system.

The following are some examples of individual solvents useful inpracticing the invention: methanol, formic acid, dimethyl sulfoxide,ethylene glycol, allyl alcohol, 2-aminoethanol; 1,1,3,3-tetramethylurea;dichloroacetic acid and trifluoroacetic acid.

Some useful solvent systems comprise mixtures of water with anothersolvent having suitably complementary solubility parameters. The mixturewith water can comprise from about 1 to about 40 percent by weightwater, based on the weight of the solvent system, from about 4 to about25 percent by weight water or another suitable proportion. If desired,the other solvent or solvents can have a hydrogen bonding parameter ofnot more than about 15 MPa^(1/2) and can have a polar bonding parameterof not more than about 18 MPa^(1/2). Some other useful solvent systemscomprise nonaqueous mixtures of solvents, including mixtures ofnon-alcoholic ones of the individual solvents mentioned above with asuitable alcoholic solvent or solvents.

The following are some examples of solvent system mixture embodiments ofthe invention wherein, in each case, the proportion of water is basedupon the weight of the solvent system:

a mixture of acetic acid and water in a proportion of from about 5percent to about 25 percent of water, the balance being acetic acid;a mixture of acetone and water in a proportion of from about 5 percentto about 25 percent of water, the balance being acetone;a mixture of dimethyl formamide (“DMF” herein) and water in a proportionof from about 5 percent to about 25 percent of water, the balance beingdimethyl formamide;a mixture of dimethyl sulfoxide and water in a proportion of from about0 percent to about 25 percent of water, optionally at least about 5percent water, the balance being dimethyl sulfoxide;a mixture of ethanol and water in a proportion of from about 0 percentto about 25 percent of water, optionally at least about 4 percent water,the balance being ethanol;a mixture of pyridine and water in a proportion of from about 1 percentto about 25 percent of water, optionally at least about 5 percent water,the balance being pyridine;a mixture of 1,1,3,3-tetramethylurea and water in a proportion of fromabout 1 percent to about 25 percent of water, optionally at least about5 percent water, the balance being acetic acid; anda mixture of dimethyl sulfoxide and ethanol in a proportion of fromabout 10 percent to about 90 percent of water, optionally at least about30 percent water, the balance being dimethyl sulfoxide, for example anapproximately 50:50 mixture.

Accordingly, a solvent system for use in diacetylenic solutionembodiments of the invention can be selected from the group consistingof methanol, formic acid, dimethyl sulfoxide, ethylene glycol,aminoethanol; 1,1,3,3-tetramethylurea; allyl alcohol, dichloroaceticacid, trifluoroacetic acid and a mixture of water with one or more ofthe foregoing solvents wherein the proportion of water based upon theweight of the solvent system is in the range of from about 1 to about 50percent.

Acetone and water and ethanol and water are further examples of aqueousmixtures that can be employed, with a similar proportion of water. Nonaqueous solvent mixtures can also be employed as solvent systems in thepractice of the invention.

One embodiment of solvent system useful in the practice of the inventioncomprises an azeotropic ethanol-water mixture comprising about 95-96percent by weight ethanol and about 4-5 percent by weight water. Theinvention includes a saturated solution of a diacetylenic monomer inthis azeotropic mixture.

If desired, other miscible solvents can be added to the foregoingmixtures to form ternary, quaternary or more complex solvent systems, aswill be apparent from, or suggested by, this disclosure. For example,ternary mixtures of water with two other solvents, for example isopropylalcohol and dimethyl sulfoxide can be employed. Suitable proportions forsuch a ternary solvent system include a proportion of up to about 25percent by weight water the balance being the two other solvents inrelative weight proportions of from about 1:2 to 2:1.

Some other useful solvent systems comprise mixtures of miscible solventswherein the polar solubility parameter and hydrogen bonding solubilityparameter of the solvent system each comprise an average of therespective parameters for the individual miscible solvents using asweighting factors the volume fraction of each solvent in the solventsystem.

Still further suitable solvent systems will be or become apparent tothose skilled in the art in light of this disclosure. For example thepolar and hydrogen-bond solubility parameters of a first prospectivesolvent can be plotted on a solubility map such as that shown in any oneof FIGS. 5-9. If the solvent lies within a desired solubility region orenvelope for a particular diacetylenic monomer, it can be expected thatthe prospective solvent can be used alone. If the solubility point forthe first prospective solvent lies outside a desired solubility regionfor the diacetylenic monomer, a solubility map can be utilized, pursuantto the invention, to select a second prospective solvent which can becombined with the first prospective solvent into a solvent systemproviding a desired solubility for the diacetylenic monomer.

It will be understood that multi-component solvent systems can be tunedto adjust the solvating power of the system for a particulardiacetylenic monomer by varying the proportions of the solvent systemcomponents.

If desired, other liquids or solids can be included in the solventsystem as will be, or will become, apparent to a person of ordinaryskill in the art. Optionally, the specified solvent or solvents cancomprise at least 50 percent by weight of the solvent system, thebalance being the other liquids and water, if employed. The otherliquids can be solvents or nonsolvents for the diacetylenic compound orcompounds to be dissolved, and can for example be another of the liquidsmentioned as solvent system components herein. Some embodiments of theinvention employ solvent systems which are free of any dissolved orundissolved solids and can formulate solutions containing only a desireddiacetylenic compound or compounds in addition to the solvent system.

Alternatively, or in addition, solid additives can be incorporated inthe solvent system, provided they are not incompatible with theobjectives of the invention, for example, a precipitation additive suchas is described and claimed in U.S. Pat. No. 7,019,171 to Prusik et al.

Diacetylenic Solutions

Some embodiments of the invention include solutions of one or morediacetylenic monomers in one of the solvent systems described herein assuitable for the purpose. Further embodiments of the invention comprisesolutions of the diacetylenic monomer in new solvent systems having asystem solubility point in the defined solubility region.

The invention also includes solutions of the diacetylenic monomer ormonomers in a solvent system embodiment of the invention in any desiredproportion up to the limits of the solvating properties of the solventsystem. For example the proportion of diacetylenic compound or compoundscan be at least 1 percent, at least 4 percent or at least 7 percent byweight based upon the weight of the solution. For many purposes, highsolubilities can be useful and the invention includes diacetylenicsolution embodiments comprising at least about 7 percent by weight ofthe solution of dissolved diacetylenic compound. Some furtherembodiments of the invention comprise diacetylenic solutions comprisingat least about 10 percent by weight of dissolved diacetylenic compound,based upon the weight of the solution.

Some examples of diacetylenic monomers that can be employed in thepractice of the invention include any diacetylenic compound capable ofproviding a visual indication, such as a color change in response toexposure to an environmental condition enabling the condition to beindicated or monitored. Some diacetylenic compounds useful asdiacetylenic monomers in the practice of the present invention canrespond to temperature, humidity, ambient atmospheric chemicalcomposition, environmental pressure, ambient radiation, another ambientcondition or combinations of these parameters.

For example, diacetylenic compounds useful as indicator agents thatprovide an irreversible indication of cumulative thermal exposure andwhich may be employed as diacetylenic monomers in practicing the presentinvention are disclosed in the Patel, Preziosi and other patents citedherein. The disclosures of Patel U.S. Pat. No. 3,999,946 at column 4,line 13, to column 5, line 48 and of Preziosi et al. U.S. Pat. No.4,788,151 at column 3, line 58, to column 4, line 62, are incorporatedby reference herein. In the disclosures incorporated from thesedocuments, references to “the invention”, “preferred”, “preferably” andthe like are to be understood to refer to the invention of therespective cited patent rather than to the invention herein.

If desired, the diacetylenic monomer compound can be selected from thegroup consisting of: 2,4-hexadiyn-1,6-bis(alkylurea) compounds whereinthe alkyl groups have from 1 to 20 carbon atoms;2,4-hexadiyn-1,6-bis(alkylurea) compounds wherein the two alkyl groupsare each independently ethyl, propyl, butyl, octyl-, dodecyl oroctadecyl; the foregoing substituted alkyl urea compounds wherein thealkyl substituents are linear; and mixtures comprising any two or moreof the foregoing diacetylenic compounds. The polymerizable diacetylenicmonomer can be symmetrically substituted, if desired.

Useful in the practice of the invention are polymerizable diacetyleniccompounds or monomers of structural formula

R¹C≡C—C≡CR²

wherein each of R¹ and R² independently is an organic substituentcompatible with providing the irreversible appearance change. Forexample, each of R¹ and R² can independently be —R⁴NHCONHR³ where R³ isalkyl having from 1 to 20 carbon atoms, optionally ethyl, propyl, butyl,octyl, dodecyl or octadecyl and R⁴ is alkyl having from 1 to 20 carbonatoms, for example, methylene, ethylene, propylene or butylene. Ifdesired, R¹ and R² can each be CH₂—NHCONHR³ and each R³ independentlycan be a straight-chain or branched saturated alkyl group. Some of theforegoing compounds are useful as active components of ambient conditionindicators, for example, time-temperature indicators.

Other diacetylenic compounds or monomers which can usefully be employedin the practice of the invention will be, or become, apparent to aperson of ordinary skill in the art. Some further examples ofdiacetylenic compounds that can be employed include diacetyleniccompounds that are sensitive to higher energy radiation but arerelatively insensitive to ambient thermal conditions such as5,7-dodecadiyn-1,12 diol bis(n-octadecyl urethane, (also referenced“4DOD” herein) and 5,7-dodecadiyn-1,12 diol bis(n-butoxycarbonylurethane.

Thus, the diacetylenic monomer can, if desired be a diacetyleniccompound having the structural formula

R³HNCONH—R⁴—C≡C—C≡C—R⁴—NHCONHR³

wherein each R³ and R⁴, independently, is as stated above.

In a further aspect, the invention provides a crystallized diacetylenicindicator agent having a crystal phase comprising a solid solution of,and/or co-crystallized from, a first diacetylenic compound and a seconddiacetylenic compound each of the first and the second diacetyleniccompounds independently having the structural formula

R³HNCONH—CH₂—C≡C—C≡C—CH₂—NHCONHR³

wherein each R³ is a straight-chain or branched saturated alkyl grouphaving from 1 to about 20 carbon atoms and can be the same or different.

Some specific examples of useful diacetylenic compounds comprise2,4-hexadiyn-1,6-bis(ethylurea), 2,4-hexadiyn-1,6-bis(propylurea) and aco-crystallized mixture, or solid solution, of2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(propylurea).

The invention includes a time-temperature indicator comprising adiacetylenic active indicator agent having a crystal phase comprising atleast one of a first and a second diacetylenic compound, each of thefirst and second diacetylenic compounds having the structural formulaR—C≡C—C≡C—R, wherein the substituent R is —CH₂NHCONHCH₂CH₃ in the firstcompound and is —CH₂NHCONH(CH₂)₂CH₃ in the second compound and furthercomprising at least one non-acetylenic compound in the crystal phase,the at least one non-acetylenic compound optionally being at least onesolvent.

Some examples of suitable diacetylenic monomers that can be employed inembodiments of diacetylenic solution according to the invention, and inother aspects of the invention, as described herein, include, ethyl-,propyl-, and octyl-substituted 2,4-hexadiyn-1,6-bis(alkylurea) compoundsas well as co-crystallized mixtures and solid solutions of two or moreof these compounds.

Recrystallization

Recrystallization of diacetylenic monomers from solution can often be auseful method of providing “fresh” active monomer that is polymer free,for providing new monomer crystal structures having desired reactivity,and for growing large crystals of the diacetylenic monomer. Knownmethods of processing diacetylenic monomers generally yield amorphous orcrystalline powders the crystals in which have maximum dimensions whichare too small for complete identification of the crystal structure byconventional X-ray crystallography.

Recrystallization processes can also be employed, or adapted, ifdesired, to purge a raw material of undesired polymeric material, forexample by separating the polymer from a solution of the monomer byfiltration, centrifugation or other suitable means.

As stated herein, care may be required in crystallizing orrecrystallizing diacetylenic compounds from heated supersaturatedsolutions to avoid time-temperature induced polymerization. Problems canarise at lower temperatures, where polymerization might be less of aproblem, owing to limited solubility of the diacetylenic monomer inknown solvents and solvent systems at lower temperatures. Accordingly,there is a need for a method of growing larger crystals, for examplecrystals having a dimension greater than about 2 mm of pure diacetyleniccompound from a supersaturated solution. Larger crystals having adimension of at least about 5 mm or at least about 10 mm would also bedesirable for some purposes.

Crystallized diacetylenic compounds according to the invention can beprepared by any suitable method for example by crystallizing thediacetylenic compound from a diacetylenic solution of the diacetyleniccompound in a solvent system. The diacetylenic solution can be preparedby dissolving the diacetylenic compound in the solvent system or byanother suitable method. If desired, the diacetylenic compound cancomprise an unpurified crystallization product,

Generally stated, the invention includes a method of recrystallizing adiacetylenic compound which method comprises heating a mixture of thediacetylenic compound in a solvent system for the diacetylenic compoundat a temperature in the range of from about 50° C. to about 100° C.,optionally on a heated water bath, to dissolve the diacetylenic compoundin the solvent system and allowing the solution to cool withoutproviding heat and without quenching to precipitate crystals of thediacetylenic compound.

One embodiment of the invention comprises a method of recrystallizing adiacetylenic monomer, for example a bis-alkylurea diacetylenic monomer,the method comprising dissolving the diacetylenic compound in a suitablesolvent providing a desired loading of solute, at an acceptable workingtemperature, and which does not react with the solute under theconditions employed. Any useful solute loading can be employed, forexample, a solute loading of at least about 1 percent by weight ofdiacetylenic compound based on the weight of the solution. Higherloadings, for example at least about 4 percent or at least about 7percent by weight, can be employed, if desired.

Heating can be employed to facilitate dissolution, if desired, forexample heating to a temperature within about 5° C. of the boiling pointof the solution. If desired, the solution can be refluxed at atemperature at or near its boiling point to vary the reactivity of thediacetylenic compound, for example as described and claimed in U.S. Pat.No. 6,924,148 to Prusik.

If desired, the raw solution can be filtered, centrifuged or otherwiseprocessed to remove particles or molecules of polymerized material orother undesired solid material that may have been present in the rawdiacetylenic monomer powder or solution.

Example 3 Recrystallization

In accordance with one embodiment of the invention, the followingprocedure can be used to recrystallize a diacetylenic monomer, forexample, 2,4-hexadiyn-1,6-bis(ethylurea), from the diacetylenic monomersolutions described herein, for example ethanol/water, or from otherdiacetylenic monomer solutions, as will be apparent to a person ofordinary skill in the art.

Preheat a water bath on a temperature controlled hotplate/stirrer to aprocess temperature of choice for example 90° C. For a 1% solution, add0.4 grams raw 2,4-hexadiyn-1,6-bis(ethylurea) and 9.6 grams 1:3 partswater/ethanol by wt. (or other solvent of choice) to a 20 mL glassscintillation vial. The quantity of solute, for example2,4-hexadiyn-1,6-bis(ethylurea), is varied according to theconcentration desired.

Heat the vial at 90° C. in a water bath and stir with magnetic stirringbar. Observe the dissolution of 2,4-hexadiyn-1,6-bis(ethylurea)diacetylenic monomer. When no particles of2,4-hexadiyn-1,6-bis(ethylurea) remain visible, switch off the heat andstirring and allow the water bath to cool. Crystals will slowlyprecipitate out of the solution.

When the water bath temperature has cooled to about 35° C., remove thevial from the bath and prepare a vacuum filtration set up with a 5micron pore size polytetrafluoroethylene filter. Filter thecrystal/solvent slurry, air-dry the product for 15 min, and thentransfer it to a glass scintillation vial.

Collect the final product and place it in a freezer at about −30° C. Ifthe crystals are still wet, as may be the case with a high boiling-pointsolvent, place the chilled crystals in a vacuum chamber (such as aFLEXI-DRY MP (trademark) lyophilizer at a pressure of <500 mTorr forabout 1-2 hours and then return it to the freezer.

A significant portion of recrystallized 2,4-hexadiyn-1,6-bis(ethylurea)can be recovered utilizing the method of Example 3 by employingsolutions of 4 percent and 7 percent 2,4-hexadiyn-1,6-bis(ethylurea) byweight, yielding long white needles of 2,4-hexadiyn-1,6-bis(ethylurea).

Another embodiment of recrystallization method according to theinvention comprises a first step of rapidly cooling a hot diacetylenicmonomer solution having a temperature of about 80° C. or higher to anintermediate temperature to limit possibly polymerization of themonomer. The method also comprises a second step of growing crystals ofa desired size from the intermediate temperature by slow or moderatecooling to a lower temperature, for example room temperature or below.The intermediate temperature can be from about 30° C. to about 50° C.,for example about 35° C. about 40° C., or other suitable temperature.Quenching with an immiscible solvent, or forced circulation or othersuitable method can be used to speed cooling in the first step, ifdesired and a water bath or the like can be employed to limit cooling inthe second step, if desired.

The invention includes a crystallized diacetylenic compound produced byany of the recrystallization methods described herein. Manytemperature-sensitive diacetylenic compounds are constantlypolymerizing, from the moment of crystallization attemperature-dependent rates. Under low-temperature storage conditions,for example from about −4° C. to about −30° C., the rate ofpolymerization may be so slow that little or no physical effects areapparent even after extended periods of time such as months or years.Higher polymerization rates at higher temperatures can, with appropriatecompounds, lead to development of color or color change. As is known,this phenomenon is useful in time-temperature indicators such as thetime-temperature indicators of the invention.

Accordingly, the crystallized diacetylenic compounds of the inventioncan, in some cases, comprise small amounts of polymerized diacetyleniccompounds, for example, up to about 0.1 percent by weight, up to about1.0 percent by weight or up to about 1.0 percent by weight, of thecrystallized diacetylenic compound can comprise polymer.

The images shown in FIG. 11 are polarized optical microscope images ofcrystals of 2,4-hexadiyn-1,6-bis(ethylurea) grown from solutions indifferent solvents under different conditions. The small crystals on theleft are obtained in conventional manner by recrystallization from hotacetic acid employing quenching with methanol to effect cooling. Thelarger crystals on the right are grown from a 25% water/ethanol mixture(a 1:3 mixture by weight) by cooling at about 1° C./min.

A 100 micron, 0.1 mm scale is shown in each photomicrograph for sizeestimation. Comparing the images, the product recrystallized from awater/ethanol mixture, pursuant to the invention, can be seen tocomprise largely of regular, long white crystals many of which havedimensions of about 0.2 mm or greater. In contrast, the crystals on theleft, precipitated from hot acetic acid, are more like a powder, beingirregular in shape and relatively small, with few, if any, crystalslarger than 0.1 mm and few, if any, needles being present.

Samples of 2,4-hexadiyn-1,6-bis(ethylurea) recrystallized from a numberof different solvent systems can be tested for their relativereactivities. For example, the ability of the diacetylenic monomer tochange color in response to time-related exposure to an environmentalcondition, such as temperature exposure, can be tested, yielding resultssuch as are shown in FIGS. 12-14, employing the method described inExample 4.

Example 4 Comparative Color-Change Reactivities

Sample pellets are prepared from crystalline diacetylenic monomer powderusing an E-Z Press 12-Ton Hydraulic Press and KBr Pellet Kit with 13 mmdie set, as supplied by International Crystal Laboratories (Garfield,N.J.). Using about 300 mg powder, a pressure of 5 to 8 tons is appliedfor 2-3 minutes. Samples of 2,4-hexadiyn-1,6-bis(ethylurea) precipitatedfrom dimethyl sulfoxide, methanol and a 4:1 by weight ethanol/watermixture are prepared. Pellets of raw 2,4-hexadiyn-1,6-bis(ethylurea)crystals (“KE raw”), precipitated from a solution in hot glacial aceticacid, using methanol as a precipitant, shortly after the2,4-hexadiyn-1,6-bis(ethylurea) was synthesized, are included ascontrols.

While being handled by the edges, an individual pellet is placed in atransparent heat-seal bag, about 50 mm by 115 mm, vacuum sealed andplaced into a heat-sealable foil pouch. The foil pouch is vacuum-sealedusing a Fuji Impulse tabletop vacuum heat sealer. The sealed foil pouchcontaining the pellets is stored in a freezer at −30° C., or othersuitable temperature, until ready for testing.

The heat-sealed foil pouch samples containing the pellets are placed ina water bath, for example a Huber circulating water bath, set toappropriate temperatures for example 37° C., 45° C. or 70° C., and agedfor suitable measured time periods such as a few days at 37° C. or a fewhours at 70° C. where the reaction proceeds more rapidly. The samplesare weighted to keep them immersed in the water during the test. Timingis started immediately after each pouch is placed into the water bath.The pouch is removed at the end of the designated test period and itsoptical density is measured.

To measure optical density the pouch is briefly immersed in a secondwater bath set at 20° C. to quench the sample and prevent further colorchange during measurement. The foil pouch is cut open leaving the pelletinside the transparent heat-sealed bag. The reaction kinetics of thediacetylenic monomer are determined by measuring the cyan opticaldensity (O.D.) of the aged pellets using an X-Rite 404 color reflectiondensitometer. The optical density can be measured on an arbitrary scaleand used for comparative indications of color change reactivity.

In order to compensate for the thickness of the pellets, which are about2 mm thick, when using the densitometer, the densitometer can be raisedon to an elevated platform of corresponding height. Some resultsobtainable are shown in FIGS. 12-14.

FIG. 14 includes a key to the solvent systems for which possible testresults are shown. This key is also applicable to FIGS. 12 and 13.

The graphs in FIGS. 12-14 plot measured color change, as changes inoptical density of samples, over time in days at 37° C., 45° C. or 70°C. respectively and can be generated by the method described in Example4. The graphs show significant differences in the reactivities of thediacetylenic monomers tested, according to the solvent employed torecrystallize the monomer.

Notably, as may be seen in FIG. 12, at 37° C.2,4-hexadiyn-1,6-bis(ethylurea) crystallized from pyridine (blacksquares) exhibits faster color change kinetics than does the raw product(stars) and also shows a faster rate of color change than the productobtained from any other solvent in the test. In addition, the pyridineproduct has a lower activation energy than the raw product, for exampleabout 19 kcal/mol compared with 23 kcal/mol for the raw control. Similareffects are manifest at 45° C., as shown in FIG. 13, and to a lesserextent at the higher temperature of 70° C., as shown in FIG. 14.

2,4-hexadiyn-1,6-bis(ethylurea) recrystallized from DMSO displaysmodestly faster reactivity than raw 2,4-hexadiyn-1,6-bis(ethylurea) at37° C., as shown in FIG. 12. However at 45° C., this effect issignificantly more pronounced, as can be seen in FIG. 13 where thereactivity profile of the DMSO product is close to that of the pyridineproduct and significantly differentiated from the other products tested.

As shown in FIG. 14, at the higher temperature of 70° C. similarrelative results can be obtained but there is less differentiationbetween products over the shorter time scale.

Overall, the several samples of diacetylenic monomer recrystallized fromthe solvents listed displayed visual response reactivities comparablewith or faster than the raw product suggesting they can be employed asactive elements in environmental condition indicators. The variation inreactivity from that of the raw product can give the formulator moreoptions for correlating an indicator with the responses of a hostproduct to be monitored.

The new solvent systems identified or provided by the invention forpreparing diacetylenic monomer solutions provides processing andrecrystallization choices that can be useful in a number of ways. Forexample, the diacetylenic monomer solutions may in some cases be usefulas indicator agents, or elements, for example when applied to asubstrate, or in other ways. As described, one or more solutions can beused to provide new crystal forms of diacetylenic monomers, for examplelarger crystals useful for X-ray or other analysis.

X-Ray Crystallographic Analysis

To facilitate understanding of and modeling of possible diacetylenicpolymerization reaction mechanisms and to help identify useful newdiacetylenic monomer processing methods it can be useful to have morestructural information about crystallized diacetylenic monomers.Pursuant to the invention, such crystallographic information can be usedto differentiate between crystallized forms of a diacetylenic compoundto identify forms that may be more useful than others for a particularapplication, for example for time-temperature, irradiation dosage orother ambient condition indicators or the like, where indicatorperformance may be sensitive to crystal structure.

Accordingly, some further embodiments of the invention compriseevaluation of crystalline powdered samples of diacetylenic monomers ofinterest by X-ray diffraction or other suitable technique. Crystallinepowders useful for crystallographic analysis can generally be obtainedby rapid quench or another fast cooling method from hot solutions of adiacetylenic monomer in acetic acid or another one of the solventsystems described or suggested herein, or from a solution in which thediacetylenic monomer has been synthesized. In general, it appears thatX-ray diffraction studies can be made on the monomer without undueinterference from minor amounts of polymer that may be present or may begenerated by the study.

In one exemplary method of X-ray analysis, a powdered sample of acrystallized diacetylenic monomer material to be analyzed is withdrawnfrom storage in a freezer, placed on a holder, and then characterizedusing X-rays of a desired fixed wavelength.

The angular variation of the intensity of diffracted radiation isrecorded using a goniometer. The recorded data are then analyzed interms of the diffraction angle, and the wavelength of the radiation usedfor crystal diffraction, to evaluate inter-atomic spacings, or d-valuesin the crystal structure in Angstrom units, “Å” (1 Å=10⁻¹⁰ m). Thedistances between planes of atoms that constitute a sample can becalculated from the goniometer data by applying Bragg's Law, in knownmanner. When values of X-ray diffraction Bragg angle 2θ are mentionedherein and the X-ray radiation is not specified, the X-ray radiationemployed is to be understood to have a wavelength of about 1.54 Å.

The characteristic set of d-spacings generated in a typical X-ray scangenerally provides a unique “fingerprint” of the material present in thecrystal sample. When suitably interpreted, by comparison with standardreference patterns and measurements, this “fingerprint” can often permitunambiguous identification of a sample material.

Example 5 Structural Analysis of Powdered Crystal (Ethylurea Compound)

Experimental X-ray diffraction patterns for a diacetylenic compound ofinterest, in this case powder crystals of raw2,4-hexadiyn-1,6-bis(ethylurea) precipitated immediately after synthesisfrom a solution of acetic acid, using methanol, for example generally asdescribed in Example A of Preziosi et al. U.S. Pat. No. 4,788,151, aregenerated using a Rigaku ULTIMA (trademark) diffractometer, providing CuK radiation at a wavelength “λ” of 1.54056 Å. Some results obtainableare shown in the lowermost diffraction pattern illustrated in FIG. 15.

The data shown in FIG. 15 are plotted as dependence of the square rootof diffracted beam intensity on the vertical axis versus 2θ degrees onthe horizontal axis, “θ” being the angle of incidence of the X-ray beam.The same axis designations are used for all X-ray diffraction patternsshown in the drawings. Unless the context indicates otherwise,references herein to a diffraction angle are to be understood to mean“2θ”.

Referring to FIG. 15, a notable feature of the diffraction pattern forraw powdered 2,4-hexadiyn-1,6-bis(ethylurea) is the presence of two highintensity peaks near 2θvalues of about 5.18 degrees and 10.39 degrees.These two intense peaks are narrow and rise sharply to intensities manytimes higher than background. The 2θ values at which the peaks are foundcorrespond with d values of 17.06 and 8.51 Å, respectively, according toBragg's law. For convenient reference, these two peaks can be indexed as001 and 002 reflections of the diacetylenic monomer crystal lattice.

Example 6 Structural Analysis of Powdered Crystal (Various Solvents)

Example 5 is repeated using crystals of 2,4-hexadiyn-1,6-bis(ethylurea)recrystallized from a number of different solvents, identified asfollows:

Sample A acetic acid Sample C 1:4 parts by weight water in dimethylsulfoxide Sample E 1:4 parts by weight water in ethyl alcohol Sample F1:4 parts by weight water in isopropyl alcoholunder relatively fast cooling conditions yielding powdery crystalprecipitates and designed to avoid undue spontaneous polymerization.Some results obtainable are shown in the diffraction patternsillustrated in FIG. 16.

Referring to FIG. 16, it can be seen that the positions and relativeintensities of the 001 and 002 peaks in a low-angle region, where 2θ isfrom about 4 degrees to about 12 degrees, are similar for allinvestigated samples. This fact may suggest that each of the crystalstructures has comparable comparable inter-planar separations in theassociated crystal plane directions. As described erein, unless thecontext indicates otherwise, 2θ angles are characterized using copper Kαradiation at about 1.542 Å.

In addition, the various diffraction pattern profiles reveal significantdifferences in a high angle region where 2θ is from about 19 degrees to24 degrees. In particular the high angle diffraction pattern can be seento vary substantially according to the recrystallization solventemployed. For example, the diffraction pattern for the sample of theknown acetic acid product, Sample A, exhibits four distinct highintensity peaks in the high angle range where 2θ is from about 19degrees to about 24 deg. The pattern for the water/isopropyl alcoholsample, Sample F exhibits only two pronounced high intensity peaks inthe high angle range, also in the range where 2θ is from about 19degrees to about 24 degrees. In contrast, the diffraction patterns for2,4-hexadiyn-1,6-bis(ethylurea) recrystallized from dimethyl sulfoxideproduct, Sample C, and water/ethyl alcohol Sample E lack significanthigh intensity peaks in the high angle range of 2θ.

Giving the height of the vertical axis shown in FIG. 16 a value of 1, itcan be determined by measurement of the figure that Sample A exhibitsfour high intensity peaks in the high angle range of from about 19degrees to about 24 degrees which exceed a value of 0.4. Sample Fexhibits two high intensity peaks in the high angle range of from about19 degrees to about 24 degrees which exceed a value of 0.4, whileneither Sample C nor Sample E exhibits any.

The X-ray diffraction data shown in FIGS. 15-17 and Table 4 areexemplary of data obtainable for 2,4-hexadiyn-1,6-bis(alkylurea)compounds. The invention includes novel crystallized diacetyleniccompounds having X-ray diffraction data as shown in the accompanyingfigures or as described herein or having peaks or other propertieswithin the angular or other ranges described herein.

Example 7 Structural Analysis of Powdered Crystal (Ethanol/Water)

Example 5 is repeated using crystals of 2,4-hexadiyn-1,6-bis(ethylurea)(“KE”) and 2,4-hexadiyn-1,6-bis(propylurea) (“KPr”) recrystallized froma 95/5 percent weight for weight ethyl alcohol/water solution withrelatively rapid cooling from a temperature near the boiling point ofthe mixture under relatively fast cooling conditions to yield powderycrystal precipitates and attempt to avoid undue spontaneouspolymerization. Some results obtainable are shown in the diffractionpatterns illustrated in FIG. 17 where the patterns for the respectivediacetylenic monomers are labeled “KE” and “KPr”.

Referring to FIG. 17, the diffraction pattern for2,4-hexadiyn-1,6-bis(ethylurea) recrystallized from 5:95 water/ethanolcan seen to be similar to the diffraction pattern for recrystallizationfrom 1:4 water/ethanol shown in FIG. 16.

The diffraction pattern for 2,4-hexadiyn-1,6-bis(propylurea), labeled“KPr”, is generally similar to that for 2,4-hexadiyn-1,6-bis(ethylurea)with the difference that the two low angle high intensity peaks areshifted downwardly to 2θ angles of about 4 degrees and 9 degrees,respectively. The 2,4-hexadiyn-1,6-bis(propylurea) pattern also lackshigh intensity peaks in the high angle range.

Some measurable 2θ values, in degrees, at which low angle high intensitypeaks, indexed 001 and 002 can be found together with correspondingcalculated d values, in Angstroms, for 2,4-hexadiyn-1,6-bis(ethylurea)and 2,4-hexadiyn-1,6-bis(propylurea), are shown in Table 4, below.

TABLE 4 Measurable 2θ, and d-values for (001) and (002) peaks of KE andKPr 2Θ₍₀₀₁₎, d₍₀₀₁₎, 2Θ₍₀₀₂₎, d₍₀₀₂₎, Compound deg Å deg Å KE 5.1617.112 10.4 8.499 KPr 4.44 19.885 8.96 9.861

Referring to Table 4, both crystallized compounds exhibit a 002 highintensity peak is at a 2θ angle which is approximately twice the 2θangle of its 001 high intensity peak. The corresponding d spacings showthe inverse relationship, namely approximately 1:2. In each case, the001 and 002 high intensity peaks can be understood to have a harmonicrelationship. d₍₀₀₁₎ for KPr (2,4-hexadiyn-1,6-bis(propylurea)) is about16% larger than d₍₀₀₁₎ for KE (2,4-hexadiyn-1,6-bis(ethylurea)). Thisdifference can be attributed to the difference in length of the twomolecules.

As stated above, a crystal of a 2,4-hexadiyn-1,6-bis(alkylurea) compoundcan exhibit an X-ray diffraction pattern comprising two high intensitypeaks at low 2θ diffraction angles of less than 12 degrees and thepattern can comprise less than four high intensity peaks at high 2θdiffraction angles in the range of from about 19 degrees to about 24degrees, when characterized using X-rays at a wavelength of about 1.54Å.

In one embodiment of the invention, the X-ray diffraction pattern of thecrystal lacks high intensity peaks at high 2θ diffraction angles in therange of from about 19 degrees to about 24 degrees. One of the two highintensity peaks at low 2θ diffraction angles can be at an angle in therange of from about 4 degrees to about 6 degrees and the other can be atan angle in the range of from about 8 degrees to about 12 degrees.

The crystal of a 2,4-hexadiyn-1,6-bis(alkylurea) compound can exhibit ad spacing corresponding with the high intensity peak at an angle in therange of from about 4 degrees to about 6 degrees. This spacing can behalf the value of the d spacing corresponding with the high intensitypeak at an angle in the range of from about 8 degrees to about 12degrees. In some cases, the two high intensity peaks at low 2θdiffraction angles of less than about 12 degrees can have a harmonicrelationship.

To provide more detailed information than can usually be obtained frompowder X-ray crystallography, structural characterization of a singlecrystal of the diacetylenic monomer under study is desirable. Anexemplary procedure, and the results obtainable are described in Example8 below.

Example 8 Structural Analysis of a Single Crystal (Ethylurea Compound)

A sample large enough for structural characterization of a singlecrystal of a diacetylenic monomer compound, using2,4-hexadiyn-1,6-bis(ethylurea) by way of example, is obtained bycrystallization from a 1:4 by weight ethanol/water solution followingthe recrystallization method described in Example 3. One embodiment ofcrystal has the shape of a needle and exhibits a well-defined growthdirection.

Structural characterization can be effected by employing a Leica MZ7polarizing microscope to identify a suitable specimen from arepresentative sampling of materials using any suitable procedure, anexample of which follows. The identified specimen is attached to a nylonloop which is fashioned to a copper mounting pin. The mounted crystal isthen placed in a cold nitrogen stream (Oxford) maintained at 110° K.

A Bruker D8 GADDS general purpose three-circle X-ray diffractometer isemployed for sample screening and data collection. The goniometer iscontrolled using GADDS software suite (Microsoft Win 2000 operatingsystem). The sample is optically centered with the aid of a video cameraso that no translations are observed as the crystal is rotated throughall positions. The detector is set at 50 mm from the crystal sample(MWPC Hi-Star Detector, 512×512 pixel). The X-ray radiation employed isgenerated from a Cu sealed X-ray tube (K_(α)=1.54184 Å with a potentialof 40 kV and a current of 40 mA) and filtered with a graphitemonochromator in the parallel mode (175 mm collimator with 0.5 mmpinholes).

A rotation exposure is taken to determine crystal quality and the X-raybeam intersection with the detector. The beam intersection coordinatesare compared to the configured coordinates and changes are madeaccordingly. If the rotation exposure indicates acceptable crystalquality, unit cell determination can be undertaken. Sixty data framesare taken at widths of 0.5° with an exposure time of 10 seconds. Over200 reflections are centered and their positions are determined. Thesereflections are used in an auto-indexing procedure to determine the unitcell. A suitable cell is found, refined by nonlinear least square andBravais lattice procedures and the results are recorded. The unit cellis verified by examination of the hkl overlays on several frames ofdata, including zone photographs. No super-cell or erroneous reflectionsshould be observed.

After careful examination of the unit cell, a standard data collectionprocedure is initiated. This procedure comprises collection of onehemisphere of data using omega scans, involving the collection over 50000.5° frames at fixed angles for φ, 2θ, and χ (2θ=−28°, χ=54.73°,2θ=−90°, χ=54.73°), while varying omega. Additional data frames arecollected to complete the data set. Each frame is exposed for 10 sec.The total data collection is performed for a duration of approximately48 hours at 110° K. No significant intensity fluctuations of equivalentreflections are observed. After data collection, the crystal is measuredcarefully for size, morphology and color.

Example 9 Structural Analysis of a Single Crystal (Propylurea Compound)

A sample large enough for structural characterization of a singlecrystal of 2,4-hexadiyn-1,6-bis(propylurea) (“KPr”) is obtained bycrystallization from a 1:4 by weight ethanol/water solution followingthe recrystallization method described in Example 3 using a similarquantity of 2,4-hexadiyn-1,6-bis(propylurea) in place of2,4-hexadiyn-1,6-bis(ethylurea).

Crystals suitable for characterization having the shape of a needle andexhibiting a well-defined growth direction are obtained. One suchsuitable crystal is characterized by X-ray analysis in accordance withthe method described in Example 8.

Crystallized Diacetylenic Compounds

The invention includes crystallized diacetylenic compounds having atriclinic or another crystal structure.

Exemplary single crystal structural data obtainable by the method ofExample 8 for 2,4-hexadiyn-1,6-bis(ethylurea) grown from 1:4water/ethanol are shown in Table 5.

TABLE 5 Data for 2,4-hexadiyn-1,6-bis(ethylurea) grown from 1:4water/ethanol Crystal system Triclinic Space group P-1 Unit celldimensions a = 4.2479(4) Å α = 88.966(7)° b = 4.6199(5) Å β = 84.663(6)°c = 16.5577(18) Å γ = 81.408(10)° Volume 319.90(6) Å³ Density(calculated) 1.299 g/cm³ Crystal size 0.25 × 0.04 × 0.01 mm³

It can be noted that the unit cell parameter c, at 16.6 Å, as isdeterminable from a single crystal experiment, is smaller than the valueobtainable from powder diffraction which is about 17.06 Å. This may beowing to different conditions of temperature or the like, or because thebroad peaks obtainable in powder diffraction patterns make precisedetermination of d values difficult, or for other reasons.

Exemplary single crystal structural data obtainable by the method ofExample 9 for 2,4-hexadiyn-1,6-bis(propylurea) grown from 1:4water/ethanol are shown in Table 6.

TABLE 6 Data for 2,4-hexadiyn-1,6-bis(propylurea) grown from 1:4water/ethanol Crystal system Monoclinic Space group P2₁/a Unit celldimensions a = 8.477 Å α = 90°. b = 4.594 Å β = 91.960(7)°. c = 19.10 Åγ = 90°. Volume 743.4 Å³ Z 2 Density (calculated) 1.244 g/cm³ Crystalsize 0.50 × 0.04 × 0.01 mm³

Tables 9-12 which appear at the end of this specification, immediatelybefore the claims, illustrate additional data obtainable by the methodof Example 9.

When characteristic data for 2,4-hexadiyn-1,6-bis(ethylurea) (“KE”) and2,4-hexadiyn-1,6-bis(propylurea) (“KPr”) are selected from Tables 5 and6 and are compared as shown in Table 7, the overall structures of thetwo compounds have significant differences.

TABLE 7 Comparison of Select Data for KE and KPr Space Group a (Å) b (Å)c (Å) α (°) β (°) γ (°) KE P-1 4.248 4.620 16.558 88.97 84.66 81.41 KPrP2₁/a 8.447 4.594 19.100 90 91.96 90

Thus, although both diacetylenic compounds exhibit primitive centeringspace group designation “P”, 2,4-hexadiyn-1,6-bis(ethylurea) has atriclinic structure with only a single center of symmetry, sometimesdesignated “Ī”. In contrast, KPr has a monoclinic structure and belongsto the space group P2₁/a, with a 2₁ screw axis and an a-glide plane,although it also has a single center of symmetry 1 (“one bar”). Thesefeatures double the length of the a-axis and the number of molecules percell.

A space group can be useful to describe the way in which molecules pack.A combination of unit cell parameters and atomic coordinates canindicate how the molecules are arranged in space in a crystal of acomplex compound such as a diacetylene monomer. The molecular spatialarrangement in the crystal can be useful for describing or predictingthe potential reactivity of a diacetylenic compound in an environmentalcondition indicator such as a time-temperature indicator.

As is known in the art, the triclinic space group comprises twostructures, P1 and P 1 (“pee-one-bar”). The monoclinic space groupcomprises thirteen structures including structure P2₁/a. One source ofinformation on space group iswww.nrl.navy.mil/lattice/spcgrp/index.html.

Notwithstanding the above-described differences, further study of theavailable data can show that the crystal structures of2,4-hexadiyn-1,6-bis(ethylurea) and 2,4-hexadiyn-1,6-bis(propylurea)have similarities with regard to characteristics relevant topolymerizability, for example, as is illustrated in Table 8 below.

TABLE 8 Comparison of Further Data for KE and KPr C1-C4 d₁ S γ₁ HydrogenH—O bond Compound (Å) (Å) (Å) (degree) bonding? distance (Å) KE, b-axis3.596 4.620 3.520 49.45° In-plane 2.095, 2.223 KPr, b-axis 3.490 4.5943.451 47.86° In-plane 2.007, 2.072

Referring to Table 8, the long unit cell axis is the c-axis, the C1-C4distance is the distance between a diyne carbon atom in one molecule andthe closest diyne carbon atom in a neighboring molecule. Numbering thecarbon atoms from 1 to 4 along the diyne group, the closest neighbor tothe C1 carbon of one molecule is the C4 carbon of its neighbor. d₁ isthe center-to-center separation between neighboring molecules which isgreater than the C1-C4 distance. “S” is the perpendicular distancebetween adjacent diacetylene rods. γ₁ (Y₁ in Table 8) is the anglebetween the short b-axis and the diacetylene rod axis and the shortb-axis is believed to be the reaction direction.

Despite differences in overall structure, it appears from the Table 8data that the structures of 2,4-hexadiyn-1,6-bis(propylurea) and2,4-hexadiyn-1,6-bis(ethylurea) structures are similar in the reactiondirection as is further described herein.

One possible model of a crystal structure for2,4-hexadiyn-1,6-bis(ethylurea) derivable from the data herein is shownin FIG. 18. A comparable model for a crystal structure for2,4-hexadiyn-1,6-bis(propylurea) is shown in FIG. 19. These structuresare consistent with available structural information for compounds inthe diacetylene family.

In FIG. 19, it can be seen that the C(7) carbon atom of one molecule of2,4-hexadiyn-1,6-bis(propylurea) is closely aligned with the C(6) carbonatom of a neighboring molecule of 2,4-hexadiyn-1,6-bis(propylurea). InFIG. 19, the carbon atoms are numbered C(1) to C(7) from each end of themolecule to the center of the molecule. A horizontal rectangular boxindicates a unit cell with an origin at the far lower left corner of thecell the “a” axis extending from the origin to the right, the “b” axisextending upwardly and the “c” axis extending forwardly, referring tothe plane of the paper or other medium in which FIG. 19 is rendered.

In the models shown in FIGS. 18 and 19, based upon the single crystalstructural data described above, the diacetylenic monomer molecules havea center-to-center separation, referring to the geometric centers ofadjacent unit cells of the crystal, of less than 4.7 Å. Also, thecenter-to-center separation is in a direction wherein solid-statepolymerization can occur.

FIG. 20 illustrates the relationship between the polymerizationdirection and the needle axis of a needle-shaped crystal of apolymerizable diacetylenic compound. The single crystal illustrated inFIG. 20 is shown schematically with a rectangular cross-section and thecrystal axes (a), (b) and (c) are shown at the lower-lefthand end of thecrystal, as viewed in the figure.

The illustrated orientation of the diacetylenic monomer molecules inrelation to the crystal axes is apparent from the marked arrow in FIG.19 which shows the direction of the short crystallographic axis b.

As may be seen from FIGS. 19 and 20, the crystallographic short axis (b)is the needle axis for 2,4-hexadiyn-1,6-bis(propylurea) and possiblyalso for 2,4-hexadiyn-1,6-bis(ethylurea).

As is marked on the arrow in the figure, FIG. 20 shows that the axis ofdichroism is believed to be parallel to the needle axis in both2,4-hexadiyn-1,6-bis(propylurea) and 2,4-hexadiyn-1,6-bis(ethylurea).Hence, it can be concluded that the direction of polymerization, in thecrystals of both compounds, is along the needle axis. The axis ofdichroism is the direction in which coloration may become apparent whenthe monomer polymerizes.

Pursuant to model structures such as are described herein, the inventionincludes crystallized diacetylenic compounds comprising hydrogen bondsbetween neighboring polymerizable diacetylenic molecules and thehydrogen bonds can extend in a direction to permit 1,4-additionpolymerization between two neighboring polymerizable diacetylenicmolecules. If desired, a hydrogen bond can extend between each of two—NH— groups in a urea group on one polymerizable diacetylenic moleculeand one ═C═O group on a neighboring polymerizable diacetylenic molecule.

In general, the diacetylenic compound can be symmetrically substituted,and when crystallized can have a crystal structure wherein thediacetylene compound has a center of symmetry and no axes or planes ofsymmetry exist which structure corresponds to a triclinic crystalstructure. Some aspects of the invention comprise diacetylenic compoundshaving a centrosymmetric crystal phase with unit cell parameters ofa=about 4.2 Å, b=about 4.6 Å, c=about 16.5 Å, α=about 89° β=about 85°,and γ=about 81° and, optionally, a triclinic structure. It will beunderstood by a person of ordinary skill in the art that the particularchoice of unit cell to represent the crystal structure for a triclinicor a monoclinic crystal may not be unique, and that other unit cells canbe employed if desired, as may be determined by selection of the cellaxis or other factors. Such other possible unit cells can bemathematically derived from a particular described or selected unit cellusing known methods and are to be understood to be inherently includedby providing information regarding a particular unit cell.

The invention includes a crystallized diacetylenic compound,2,4-hexadiyn-1,6-bis(ethylurea), having the structural formula

CH₃CH₂HNCONH—CH₂—C≡C—C≡C—CH₂—NHCONHCH₂CH₃

or

CH₃CH₂CH₂HNCONH—CH₂—C≡C—C≡C—CH₂—NHCONHCH₂CH₂CH₃

and having a triclinic crystal structure, which can have theabove-stated unit cell parameters.

The proportion of the crystallized diacetylenic compound that comprisesa crystallized diacetylenic compound having a triclinic crystalstructure can be selected from the group consisting of at least about 50percent, at least about 80 percent and at least about 90 percent, theproportions being by weight based upon the total weight of diacetyleniccompound.

The crystallized diacetylenic compound can have any desired purity, forexample a purity in a range selected from the group of ranges consistingof: at least about 90 percent by weight pure; at least about 95 percentby weight pure; at least about 98 percent by weight pure; at least about99 percent by weight pure; and at least about 99.8 percent by weightpure. The pure crystallized compound can optionally include acrystallization solvent or solvents. If desired, a recrystallizationprocess can be repeated one or more times to increase the purity of thediacetylenic compound, using the same or a different solvent system.

The invention also includes time-temperature indicators comprising acrystal phase containing a diacetylenic compound of structure

[CH₃(CH₂)_(n)NHCONH(CH₂)_(m)C≡C—]₂.

wherein “n” can be an odd number (integer) from 1 to 19 and “m” can bean odd number (integer) from 1 to 7. A first diacetylenic molecule ofthe diacetylenic compound can polymerize by reaction with diacetylenegroups in two neighboring diacetylenic molecules. Also, the two ═C═Ogroups on the first diacetylenic molecule can each hydrogen bond to two—NH— groups in a neighboring diacetylenic molecule. The crystal phasecan be triclinic and optionally can have a center of symmetry.

In some embodiments of this time-temperature indicator, the tricliniccrystal phase comprises two or more different diacetylenic compoundshaving the structure stated. In each diacetylenic molecule, “m” is anodd number. In one of the diacetylenic compounds “n” is an odd or evennumber having a first value and in another of the diacetylenic compounds“n” is also an odd or even number respectively and has a second value,the second value being a value different from the first value. In oneembodiment of the invention, “n” is odd in both or all the diacetyleniccompounds. In another embodiment “n” is even both or all thediacetylenic compounds. While the invention is not to be limited by anyparticular theory, it is believed that the zig-zag conformation oftenadopted by alkyl and alkylene groups may favor the described numericalselections of “m” and “n”. Suitable examples of compounds having thesestructural characteristics will be, or become, apparent to a person ofordinary skill in the art in light of this disclosure.

The invention has been described largely with reference to diacetyleniccompounds that are potentially useful for providing an appearance changein environmental monitors or indicators as a result of spontaneouspolymerization under the monitored environmental condition orconditions. It will be understood that such useful properties aredesirable in the products of the methods of the invention, but may notnecessarily be possessed by the starting materials. Thus, it iscontemplated that, in some cases, a diacetylenic compound having little,if any, useful indicator activity, in the raw state may be modified by amethod or process of the invention to yield a product having usefulindicator activity.

The invention also comprises any useful combination of two or morecompatible ones of the various aspects, embodiments or features of theproducts and methods of the invention disclosed herein. A person ofordinary skill in the art will understand that many of the features orelements of the various embodiments and aspects of the inventiondisclosed herein can be used in combination one with another.

The entire disclosure of each and every United States patent and patentapplication, each foreign and international patent publication, of eachother publication and of each unpublished patent application that isspecifically referenced in this specification is hereby incorporated byreference herein, in its entirety.

The foregoing detailed description is to be read in light of and incombination with the preceding background and invention summarydescriptions wherein partial or complete information regarding the bestmode of practicing the invention, or regarding modifications,alternatives or useful embodiments of the invention may also be setforth or suggested, as will be apparent to one skilled in the art.Should there appear to be conflict between the meaning of a term as usedin the written description of the invention in this specification andthe usage in material incorporated by reference from another document,the meaning as used herein is intended to prevail.

Throughout the description, where compositions are described as having,including, or comprising specific components, or where processes aredescribed as having, including, or comprising specific process steps, itis contemplated that compositions of the present invention can alsoconsist essentially of, or consist of, the recited components, and thatthe processes of the present invention can also consist essentially of,or consist of, the recited processing steps. It should be understoodthat the order of steps or order for performing certain actions isimmaterial so long as the invention remains operable. Moreover, two ormore steps or actions may be conducted simultaneously. In addition, allproportions recited herein are to be understood to be proportions byweight, based upon the weight of the relevant composition, unless thecontext indicates otherwise.

While illustrative embodiments of the invention have been describedabove, it is, of course, understood that many and various modificationswill be apparent to those of ordinary skill in the relevant art, or maybecome apparent as the art develops, in the light of the foregoingdescription. Such modifications are contemplated as being within thespirit and scope of the invention or inventions disclosed in thisspecification.

TABLE 9 Atomic coordinates (×10⁴) and equivalent isotropic displacementparameters (Å² × 10³) for KPr. U(eq) is defined as one third of thetrace of the orthogonalized U^(ij) tensor. x y z U(eq) O(1) 2882(1)7863(4) 4898(2) 41(1) N(1) 2476(1) 3520(6) 5799(3) 41(1) N(2) 3450(1)3675(5) 4292(3) 40(1) C(1)  679(2) 6960(7) 6386(4) 52(1) C(2) 1276(2)5519(7) 5517(4) 46(1) C(3) 1899(1) 4826(6) 6607(3) 40(1) C(4) 2930(1)5161(6) 4986(3) 36(1) C(5) 3909(1) 5186(6) 3219(4) 38(1) C(6) 4388(2)7234(6) 4019(4) 38(1) C(7) 4780(2) 9002(6) 4634(4) 38(1)

TABLE 10 Bond lengths [Å] and angles [°] for KPr. O(1)—C(4)  1.247(3)N(1)—C(4)  1.356(4) N(1)—C(3)  1.446(4) N(1)—H(1)  0.79(4) N(2)—C(4) 1.356(4) N(2)—C(5)  1.460(4) N(2)—H(2)  1.08(5) C(1)—C(2)  1.529(4)C(1)—H(1A)  0.9800 C(1)—H(1B)  0.9800 C(1)—H(1C)  0.9800 C(2)—C(3) 1.516(4) C(2)—H(2A)  0.9900 C(2)—H(2B)  0.9900 C(3)—H(3A)  0.9900C(3)—H(3B)  0.9900 C(5)—C(6)  1.463(4) C(5)—H(5A)  0.9900 C(5)—H(5B) 0.9900 C(6)—C(7)  1.211(4) C(7)—C(7)#1  1.377(6) C(7)—C(6)#2  3.452(4)C(4)—N(1)—C(3) 121.4(3) C(4)—N(1)—H(1) 116(2) C(3)—N(1)—H(1) 122(2)C(4)—N(2)—C(5) 119.7(3) C(4)—N(2)—H(2) 121(2) C(5)—N(2)—H(2) 117(2)C(2)—C(1)—H(1A) 109.5 C(2)—C(1)—H(1B) 109.5 H(1A)—C(1)—H(1B) 109.5C(2)—C(1)—H(1C) 109.5 H(1A)—C(1)—H(1C) 109.5 H(1B)—C(1)—H(1C) 109.5C(3)—C(2)—C(1) 112.4(3) C(3)—C(2)—H(2A) 109.1 C(1)—C(2)—H(2A) 109.1C(3)—C(2)—H(2B) 109.1 C(1)—C(2)—H(2B) 109.1 H(2A)—C(2)—H(2B) 107.9N(1)—C(3)—C(2) 113.2(2) N(1)—C(3)—H(3A) 108.9 C(2)—C(3)—H(3A) 108.9N(1)—C(3)—H(3B) 108.9 C(2)—C(3)—H(3B) 108.9 H(3A)—C(3)—H(3B) 107.8O(1)—C(4)—N(1) 122.5(3) O(1)—C(4)—N(2) 121.9(3) N(1)—C(4)—N(2) 115.6(3)N(2)—C(5)—C(6) 113.3(2) N(2)—C(5)—H(5A) 108.9 C(6)—C(5)—H(5A) 108.9N(2)—C(5)—H(5B) 108.9 C(6)—C(5)—H(5B) 108.9 H(5A)—C(5)—H(5B) 107.7C(7)—C(6)—C(5) 177.5(3) C(6)—C(7)—C(7)#1 178.7(4) C(6)—C(7)—C(6)#2 81.8(2) C(7)#1—C(7)—C(6)#2  97.8(2) Symmetry transformations used togenerate equivalent atoms: #1−x + 1, −y + 2, −z + 1 #2−x + 1, −y + 1,−z + 1

TABLE 11 Anisotropic displacement parameters (Å² × 10³) for KPr. Theanisotropic displacement factor exponent takes the form: −2π²[h² a *²U¹¹ + . . . + 2 h k a* b* U¹²] U¹¹ U²² U³³ U²³ U¹³ U¹² O(1) 57(1) 13(1)54(1) −2(1) 11(1) 1(1) N(1) 55(2) 17(2) 54(2) 2(1) 16(1) 2(1) N(2) 54(2)19(1) 47(2) 0(1) 15(1) 1(1) C(1) 56(2) 34(2) 65(2) −3(2) 5(2) 3(1) C(2)57(2) 32(2) 50(2) −3(2) 13(2) 2(1) C(3) 55(2) 21(2) 43(2) 1(2) 11(1)0(1) C(4) 51(2) 20(2) 37(2) −1(1) 8(1) 1(1) C(5) 50(2) 17(2) 48(2) 0(1)12(1) −2(1) C(6) 49(2) 19(2) 47(2) 4(1) 14(1) 5(1) C(7) 53(2) 16(2)46(2) 7(1) 11(1) 3(1)

TABLE 12 Hydrogen coordinates (×10⁴) and isotropic displacementparameters (Å² × 10³) for KPr. x y z U(eq) H(1) 2508(15) 1810(90)5700(40) 53(11) H(2) 3449(19) 1320(110) 4260(50) 96(13) H(1A)  291 73835636 77 H(1B)  847 8777 6872 77 H(1C)  518 5644 7208 77 H(2A) 1102 36975018 55 H(2B) 1427 6833 4668 55 H(3A) 2064 6643 7125 47 H(3B) 1748 34817441 47 H(5A) 3617 6258 2425 46 H(5B) 4187 3727 2650 46

1-39. (canceled)
 40. A time-temperature indicator comprising: acrystallized diacetylenic compound capable of polymerizing in the solidstate to provide an irreversible appearance change in an environmentalcondition indicator; and a substrate onto which the crystallizeddiacetylenic compound is applied; wherein a change in appearance of thecrystallized diacetylenic compound is detectable in a manner that isuseful to indicate an ambient condition; wherein the crystallizeddiacetylenic compound is symmetrically substituted and having thestructural formula:R′NHCONH—R—C≡C—C≡C—R—NHCONHR′ wherein R is methylene, ethylene,propylene or butylene, R′ is a linear alkyl group having from 1 to 21carbon atoms, the crystallized diacetylenic compound having a crystalstructure wherein the crystallized diacetylenic compound molecules havea center-to-center separation, referring to the geometric centers ofdiacetylene units in adjacent molecules, of less than 4.7 Å, thecenter-to-center separation being in a direction wherein solid-statepolymerization can occur.
 41. The time-temperature indicator of claim 40wherein the center-to-center separation corresponds to a unit cellrepeat distance of the crystallized diacetylenic compound.
 42. Thetime-temperature indicator of claim 40 wherein R′ is butyl, octyl,dodecyl or octadecyl.
 43. The time-temperature indicator of claim 40,wherein the crystallized diacetylinic compound comprises two hydrogenbonds for each NHCONH urea group, each one of the two hydrogen bondsextending between one of the two NH groups in a urea group in onepolymerizable diacetylenic molecule and a C═O group in an adjacentpolymerizable diacetylenic molecule.
 44. The time-temperature indicatorof claim 40, wherein the crystallized diacetylinic compound has atriclinic crystal structure including a center of symmetry wherein noaxes or planes of symmetry exist.
 45. The time-temperature indicator ofclaim 40, wherein the crystallized diacetylinic compound has amonoclinic crystal structure.
 46. The time-temperature indicator ofclaim 40, wherein the crystallized diacetylinic compound has a purity ofat least about 99 percent by weight.
 47. The time-temperature indicatorof claim 40 comprising at least one non-acetylenic compound in a crystalphase of the diacetylenic compound.
 48. (canceled)
 49. (canceled)
 50. Atime-temperature indicator comprising a crystallized diacetyleniccompound according to claim 40 wherein the crystallized diacetyleniccompound is 2,4-hexadiyn-1,6-bis(ethylurea).
 51. A time-temperatureindicator comprising a crystallized diacetylenic compound according toclaim 40 wherein the crystallized diacetylenic compound is2,4-hexadiyn-1,6-bis(propylurea).
 52. A time-temperature indicatorcomprising a solid phase composition including a crystallizeddiacetylenic compound disposed on a substrate; wherein a change inappearance of the crystallized diacetylenic compound is detectable;having the structural formula[CH₃(CH₂)_(n)NHCONH(CH₂)_(m)C≡C—]₂ wherein: “m” is an odd number from 1to 7; “n” is an odd number from 1 to 19; and the solid phase comprises atriclinic space group P-1; the crystallized diacetylenic compound beingcapable of polymerizing to provide a color change in response to ambientheat and comprising two hydrogen bonds for each NHCONH urea group, eachone of the two hydrogen bonds extending between one of the two NH groupsin a urea group in one polymerizable diacetylenic molecule and a C═Ogroup in an adjacent polymerizable diacetylenic molecule.
 53. Atime-temperature indicator comprising a solid phase compositionincluding a crystallized diacetylenic compound and a substrate, whereinthe crystallized diacetylenic compound has the structural formula[CH₃(CH₂)_(n)NHCONH(CH₂)_(m)C≡C—]₂ wherein: “m” is an odd number from 1to 7; “n” is an even number from 2 to 20; and the solid phase comprisesa monoclinic space group P2₁/a or space group P2₁/c wherein, in eachspace group, the b axis is the 2₁ axis; the crystallized diacetyleniccompound molecule being capable of polymerizing to provide a colorchange in response to ambient heat and comprising two hydrogen bonds foreach NHCONH urea group, each one of the two hydrogen bonds extendingbetween one of the two NH groups in a urea group in one polymerizablediacetylenic molecule and a C═O group in an adjacent polymerizablediacetylenic molecule. 54-62. (canceled)
 63. The time temperatureindicator of claim 40, wherein the crystallized diacetylenic compound iscrystallized from pyridine, methanol, dimethyl sulfoxide, or a mixtureof water and ethanol.
 64. The time temperature indicator of claim 40,wherein the crystallized diacetylenic compound is crystallized from amixture of water and ethanol.
 65. The time temperature indicator ofclaim 52, wherein the crystallized diacetylenic compound is crystallizedfrom pyridine, methanol, dimethyl sulfoxide, or a mixture of water andethanol.
 66. The time temperature indicator of claim 52, wherein thecrystallized diacetylenic compound is crystallized from a mixture of 25%water in ethanol.
 67. The time temperature indicator of claim 52,wherein the crystallized diacetylenic compound is crystallized frompyridine, methanol, dimethyl sulfoxide, or a mixture of water andethanol.
 68. The time temperature indicator of claim 52, wherein thecrystallized diacetylenic compound is crystallized from a mixture ofwater and ethanol.